SEARCH
Search Details
Kohji Moriishi
| Institute for Genetic Medicine Molecular Pathogenesis | Professor |
Career
■ CareerCommittee Memberships
Research activity information
■ Awards- May 2026, SpringerNature, Editor of Distinction Awards, Author Service Award
Kohji Moriishi - Apr. 2025, 一般財団法人イスクラワクチン・医療基金, 多ヶ谷勇記念ワクチン研究イスクラ奨励賞
C型肝炎ウイルス（HCV)に近縁なヘパシウイルスを用いたサロゲート感染モデルの開発
森石 恆司
- Generation of a HiBiT-expressing recombinant rat hepacivirus supporting both in vivo and in vitro infection
Yasunori Akaike; Tomohisa Tanaka; Hirotake Kasai; Atsuya Yamashita; Yoshiharu Matsuura; Kohji Moriishi
PLOS Pathogens, 22, 4, e1014127, e1014127, Public Library of Science (PLoS), 08 Apr. 2026, [Peer-reviewed], [Corresponding author]
English, Scientific journal, The lack of immuno-competent animal models of hepatitis C virus (HCV) infection has been an obstacle to vaccine development and research on immune responses. Hepacivirus ratti (Norway rat hepacivirus-1: NRHV1) is a virus closely related to HCV that specifically infects the liver and induces hepatocellular carcinoma in rats, making it a promising surrogate model for HCV. NRHV1 expressing a reporter gene serves as a powerful tool for analyzing the in vivo dynamics and pathogenicity mechanisms of NRHV1. In this study, we developed a reporter NRHV1 capable of infection and replication in both immunodeficient mice and cultured cells and established a platform for generating diverse reporter viruses. A reporter virus containing the HiBiT gene in the coding region of NS5A domain III was constructed using circular polymerase extension reaction (CPER). Infection with this reporter virus led to HiBiT activity in infected cells and the activity was correlated with the amount of intracellular viral RNA. In addition, this reporter virus established persistent infection in NOD-SCID mice and led to the generation of HiBiT activity in the livers of infected mice, although loss of the HiBiT gene was observed in some mice. Furthermore, reporter virus recovered from infected mice could infect and generate HiBiT activity in cultured cells. These results demonstrate that the reporter virus can infect hepatocytes in vivo and in vitro . This platform provides a versatile tool for in vitro quantitative antiviral screening and for exploring viral infection dynamics in vivo , although further studies will be required to improve the long-term stability of the HiBiT reporter. - Identification of claudin-3 as an entry factor for rat hepacivirus
Tomohisa Tanaka; Yasunori Akaike; Hirotake Kasai; Atsuya Yamashita; Yoshiharu Matsuura; Kohji Moriishi
Proceedings of the National Academy of Sciences, 122, 40, Proceedings of the National Academy of Sciences, 02 Oct. 2025
Scientific journal, Approximately 58 million people worldwide are believed to be infected with hepatitis C virus (HCV), a major causative agent of chronic liver diseases. Hepacivirus ratti strain rn-1, which was discovered from Rattus norvegicus (Norway rat) and designated Norway rat hepacivirus 1 (NRHV1), shares similar properties with HCV in terms of genetic homology, target cell tropism, pathogenicity, and the immune response. In vivo infection systems for NRHV1 will help overcome the challenges in HCV research for vaccine development. However, the virological characteristics of NRHV1, such as the mechanisms of cell entry, remain largely unexplored, in part owing to a paucity of cell culture systems for NRHV1. Here, we identified the host factors that facilitate NRHV1 entry by profiling the gene expression of two cell lines with different susceptibilities to NRHV1 infection. NRHV1 employs rodent orthologues of HCV entry factors, including scavenger receptor class BI, CD81, and occludin, and utilizes claudin-3 (CLDN3) but not claudin-1. The expression of rat and mouse, but not human, CLDN3 facilitates the entry of NRHV1 into murine cell lines that are nonsusceptible to NRHV1 infection. The host-specific cell entry of CLDN3 is determined by two amino acid residues, Ile 44 and Trp 46 , in extracellular loop 1. These findings suggest that CLDN3 serves as an entry factor for rat hepacivirus. - NEDD4-binding protein 1 suppresses hepatitis B virus replication by regulating viral RNAs
Nobuhiro Kobayashi; Saori Suzuki; Yuki Sakamoto; Rigel Suzuki; Kento Mori; Yume Kosugi; Tomoya Saito; Yuan Ma; Lihan Liang; Takuma Izumi; Kisho Noda; Daisuke Okuzaki; Yumi Kanegae; Sanae Hayashi; Yasuhito Tanaka; Atsuya Yamashita; Kohji Moriishi; Yoshiharu Matsuura; Osamu Takeuchi; Tomokazu Tamura; Akinobu Taketomi; Takasuke Fukuhara
Journal of General Virology, 106, 3, 2025
Scientific journal - Berberine promotes K48-linked polyubiquitination of HNF4α, leading to the inhibition of HBV replication.
Atsuya Yamashita; Hirotake Kasai; Shinya Maekawa; Tomohisa Tanaka; Yasunori Akaike; Akihide Ryo; Nobuyuki Enomoto; Kohji Moriishi
Antiviral research, 232, 106027, 106027, 01 Nov. 2024, [International Magazine]
English, Scientific journal, The current antiviral agents for the treatment of chronic infection with hepatitis B virus (HBV) do not completely remove covalently closed circular DNA (cccDNA) and integrated viral DNA fragments from patients. Berberine is an isoquinoline alkaloid extracted from various plants and has been reported to inhibit the replication of various types of DNA. In this study, we tested the effects of berberine and its derivatives on HBV infection. Berberine inhibited viral core promoter activity at the highest level among the compounds tested and suppressed HBV production and cccDNA synthesis in primary human hepatocytes and HBV-infected HepG2-NTCP cells at an EC50 value of 3.6 μM and a CC50 value of over 240.0 μM. Compared with other viral promoter activities, berberine treatment potently downregulated core promoter activity and reduced protein levels, but not RNA levels, of hepatic nuclear factor 4α (HNF4α), which primarily enhances enhancer II/core promoter activity. Furthermore, berberine treatment enhanced K48-linked, but not K63-linked, polyubiquitination and subsequent proteasome-dependent degradation of HNF4α. These results suggest that berberine enhances the polyubiquitination- and proteasome-dependent degradation of HNF4α and then inhibits HBV replication via the suppression of core promoter activity. The development of antiviral agents based on berberine may contribute to the amelioration of HBV-related disorders, regardless of the presence of residual cccDNA or integrated viral DNA fragments. - HCV infection activates the proteasome via PA28γ acetylation and heptamerization to facilitate the degradation of RNF2, a catalytic component of polycomb repressive complex 1.
Hirotake Kasai; Atsuya Yamashita; Yasunori Akaike; Tomohisa Tanaka; Yoshiharu Matsuura; Kohji Moriishi
mBio, e0169124, 27 Sep. 2024, [International Magazine]
English, Scientific journal, We previously reported that hepatitis C virus (HCV) infection or HCV core protein expression induces HOX gene expression by impairing histone H2A monoubiquitination via a proteasome-dependent reduction in the level of RNF2, a key catalytic component of polycomb repressive complex 1 (H. Kasai, K. Mochizuki, T. Tanaka, A. Yamashita, et al., J Virol 95:e01784-20, 2021, https://doi.org/10.1128/jvi.01784-20). In this study, we aimed to investigate the mechanism by which HCV infection accelerates RNF2 degradation. Yeast two-hybrid screening and an immunoprecipitation assay revealed that RNF2 is a PA28γ-binding protein. The proteasome activator PA28γ destabilized the RNF2 protein in a proteasome-dependent manner, since RNF2 degradation was impaired by PA28γ knockout or MG132 treatment. HCV infection or core protein expression reduced the levels of RNF2 and histone H2A K119 monoubiquitination and induced the expression of HOX genes in the presence of PA28γ, while PA28γ knockout reversed these changes. Treatment with a lysine acetyltransferase inhibitor inhibited the acetylation of PA28γ at K195 and the degradation of the RNF2 protein, while treatment with a lysine deacetylase inhibitor accelerated these events in a PA28γ-dependent manner. RNF2 protein degradation was increased by expression of the acetylation mimetic PA28γ mutant but not by expression of the acetylation-defective mutant or the proteasome activation-defective mutant. Furthermore, HCV infection or core protein expression facilitated the interaction between PA28γ and the lysine acetyltransferase CBP/p300 and then accelerated PA28γ acetylation and heptazmerization to promote RNF2 degradation. These data suggest that HCV infection accelerates the acetylation-dependent heptamerization of PA28γ to increase the proteasomal targeting of RNF2.IMPORTANCEHCV is a causative agent of HCV-related liver diseases, including hepatic steatosis, cirrhosis, and hepatocellular carcinoma. PA28γ, which, in heptameric form, activates the 20S core proteasome for the degradation of PA28γ-binding proteins, is responsible for HCV-related liver diseases. HCV core protein expression or HCV infection accelerates RNF2 degradation, leading to the induction of HOX gene expression via a decrease in the level of H2Aub on HOX gene promoters. However, the mechanism of RNF2 degradation in HCV-infected cells has not been clarified. The data presented in this study suggest that PA28γ acetylation and heptamerization are promoted by HCV infection or by core protein expression to activate the proteasome for the degradation of RNF2 and are responsible for HCV propagation. This study provides novel insights valuable for the development of therapies targeting both HCV propagation and HCV-related diseases. - SARS-CoV-2 papain-like protease inhibits ISGylation of the viral nucleocapsid protein to evade host anti-viral immunity.
Aulia Fitri Rhamadianti; Takayuki Abe; Tomohisa Tanaka; Chikako Ono; Hisashi Katayama; Yoshiteru Makino; Lin Deng; Chieko Matsui; Kohji Moriishi; Fumi Shima; Yoshiharu Matsuura; Ikuo Shoji
Journal of virology, 98, 9, e0085524, 17 Sep. 2024, [International Magazine]
English, Scientific journal, A severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes mild-to-severe respiratory symptoms, including acute respiratory distress. Despite remarkable efforts to investigate the virological and pathological impacts of SARS-CoV-2, many of the characteristics of SARS-CoV-2 infection still remain unknown. The interferon-inducible ubiquitin-like protein ISG15 is covalently conjugated to several viral proteins to suppress their functions. It was reported that SARS-CoV-2 utilizes its papain-like protease (PLpro) to impede ISG15 conjugation, ISGylation. However, the role of ISGylation in SARS-CoV-2 infection remains unclear. We aimed to elucidate the role of ISGylation in SARS-CoV-2 replication. We observed that the SARS-CoV-2 nucleocapsid protein is a target protein for the HERC5 E3 ligase-mediated ISGylation in cultured cells. Site-directed mutagenesis reveals that the residue K374 within the C-terminal spacer B-N3 (SB/N3) domain is required for nucleocapsid-ISGylation, alongside conserved lysine residue in MERS-CoV (K372) and SARS-CoV (K375). We also observed that the nucleocapsid-ISGylation results in the disruption of nucleocapsid oligomerization, thereby inhibiting viral replication. Knockdown of ISG15 mRNA enhanced SARS-CoV-2 replication in the SARS-CoV-2 reporter replicon cells, while exogenous expression of ISGylation components partially hampered SARS-CoV-2 replication. Taken together, these results suggest that SARS-CoV-2 PLpro inhibits ISGylation of the nucleocapsid protein to promote viral replication by evading ISGylation-mediated disruption of the nucleocapsid oligomerization.IMPORTANCEISG15 is an interferon-inducible ubiquitin-like protein that is covalently conjugated to the viral protein via specific Lys residues and suppresses viral functions and viral propagation in many viruses. However, the role of ISGylation in SARS-CoV-2 infection remains largely unclear. Here, we demonstrated that the SARS-CoV-2 nucleocapsid protein is a target protein for the HERC5 E3 ligase-mediated ISGylation. We also found that the residue K374 within the C-terminal spacer B-N3 (SB/N3) domain is required for nucleocapsid-ISGylation. We obtained evidence suggesting that nucleocapsid-ISGylation results in the disruption of nucleocapsid-oligomerization, thereby suppressing SARS-CoV-2 replication. We discovered that SARS-CoV-2 papain-like protease inhibits ISG15 conjugation of nucleocapsid protein via its de-conjugating enzyme activity. The present study may contribute to gaining new insight into the roles of ISGylation-mediated anti-viral function in SARS-CoV-2 infection and may lead to the development of more potent and selective inhibitors targeted to SARS-CoV-2 nucleocapsid protein. - Identification of neutralizing epitopes in the preS2 domain of the hepatitis B virus.
Keigo Yato; Mami Matsuda; Kento Fukano; Tomohisa Tanaka; Kohji Moriishi; Hironori Nishitsuji; Kunitada Shimotohno; Koji Tamura; Takaji Wakita; Masamichi Muramatsu; Takanobu Kato; Ryosuke Suzuki
Virus research, 323, 199014, 199014, 02 Jan. 2023, [International Magazine]
English, Scientific journal, Hepatitis B virus (HBV) infection is a major public health problem. The sodium taurocholate cotransporting polypeptide (NTCP) has been identified as an essential HBV receptor. Human hepatocytes are infected with HBV via binding between the preS1 region of the HBV large envelope protein and the NTCP. However, the role of preS2 in HBV entry is not well understood. In this study, we induced anti-preS2 serum in mice by DNA immunization, and showed that the resulting antiserum neutralized HBV infectivity. Competition assays using overlapping peptides suggested that the neutralizing epitope is located in the N-terminal region of preS2. In addition, monoclonal antibodies targeting the N-terminal region of preS2 neutralized HBV infectivity, indicating that these domains are critical epitopes for viral neutralization. These findings provide new insights into the HBV entry machinery while suggesting a novel modality for the prevention and treatment of HBV infection. - Neutralization of hepatitis B virus with vaccine-escape mutations by hepatitis B vaccine with large-HBs antigen
Ayaka Washizaki; Asako Murayama; Megumi Murata; Tomoko Kiyohara; Keigo Yato; Norie Yamada; Hussein Hassan Aly; Tomohisa Tanaka; Kohji Moriishi; Hironori Nishitsuji; Kunitada Shimotohno; Yasumasa Goh; Ken J. Ishii; Hiroshi Yotsuyanagi; Masamichi Muramatsu; Koji Ishii; Yoshimasa Takahashi; Ryosuke Suzuki; Hirofumi Akari; Takanobu Kato
Nature Communications, 13, 1, Springer Science and Business Media LLC, 05 Sep. 2022
Scientific journal, Abstract
Although the current hepatitis B (HB) vaccine comprising small-HBs antigen (Ag) is potent and safe, attenuated prophylaxis against hepatitis B virus (HBV) with vaccine-escape mutations (VEMs) has been reported. We investigate an HB vaccine consisting of large-HBsAg that overcomes the shortcomings of the current HB vaccine. Yeast-derived large-HBsAg is immunized into rhesus macaques, and the neutralizing activities of the induced antibodies are compared with those of the current HB vaccine. Although the antibodies induced by the current HB vaccine cannot prevent HBV infection with VEMs, the large-HBsAg vaccine-induced antibodies neutralize those infections. The HBV genotypes that exhibited attenuated neutralization via these vaccines are different. Here, we show that the HB vaccine consisting of large-HBsAg is useful to compensate for the shortcomings of the current HB vaccine. The combined use of these HB vaccines may induce antibodies that can neutralize HBV strains with VEMs or multiple HBV genotypes. - Hydrophobic Alpha-Helical Short Peptides in Overlapping Reading Frames of the Coronavirus Genome
Takashi Okura; Kazuya Shirato; Masatoshi Kakizaki; Satoko Sugimoto; Shutoku Matsuyama; Tomohisa Tanaka; Yohei Kume; Mina Chishiki; Takashi Ono; Kohji Moriishi; Masashi Sonoyama; Mitsuaki Hosoya; Koichi Hashimoto; Katsumi Maenaka; Makoto Takeda
Pathogens, 11, 8, 877, 877, MDPI AG, 03 Aug. 2022
Scientific journal, In this study, we show that the coronavirus (CoV) genome may encode many functional hydrophobic alpha-helical peptides (HAHPs) in overlapping reading frames of major coronaviral proteins throughout the entire viral genome. These HAHPs can theoretically be expressed from non-canonical sub-genomic (sg)RNAs that are synthesized in substantial amounts in infected cells. We selected and analyzed five and six HAHPs encoded in the S gene regions of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and Middle East respiratory syndrome coronavirus (MERS-CoV), respectively. Two and three HAHPs derived from SARS-CoV-2 and MERS-CoV, respectively, specifically interacted with both the SARS-CoV-2 and MERS-CoV S proteins and inhibited their membrane fusion activity. Furthermore, one of the SARS-CoV-2 HAHPs specifically inhibited viral RNA synthesis by accumulating at the site of viral RNA synthesis. Our data show that a group of HAHPs in the coronaviral genome potentially has a regulatory role in viral propagation. - Novel Neplanocin A Derivatives as Selective Inhibitors of Hepatitis B Virus with a Unique Mechanism of Action
Masaaki Toyama; Koichi Watashi; Masanori Ikeda; Atsuya Yamashita; Mika Okamoto; Kohji Moriishi; Masamichi Muramatsu; Takaji Wakita; Ashoke Sharon; Masanori Baba
Antimicrobial Agents and Chemotherapy, American Society for Microbiology, 23 May 2022
Scientific journal, Novel neplanocin A derivatives have been identified as potent and selective inhibitors of hepatitis B virus (HBV) replication in vitro . These include (1S,2R,5R)-5-(5-bromo-4-methyl-7H-pyrrolo[2,3-d]-pyrimidin-7-yl)-3-(hydroxymethyl)cyclopent-3-ene-1,2-diol (AR-II-04-26) and (1S,2R,5R)-5-(4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-3-(hydroxylmethyl)cyclopent-3-ene-1,2-diol (MK-III-02-03). - SARS-CoV-2 ORF6 disrupts nucleocytoplasmic trafficking to advance viral replication.
Yoichi Miyamoto; Yumi Itoh; Tatsuya Suzuki; Tomohisa Tanaka; Yusuke Sakai; Masaru Koido; Chiaki Hata; Cai-Xia Wang; Mayumi Otani; Kohji Moriishi; Taro Tachibana; Yoichiro Kamatani; Yoshihiro Yoneda; Toru Okamoto; Masahiro Oka
Communications biology, 5, 1, 483, 483, 19 May 2022, [International Magazine]
English, Scientific journal, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ORF6 is an antagonist of interferon (IFN)-mediated antiviral signaling, achieved through the prevention of STAT1 nuclear localization. However, the exact mechanism through which ORF6 prevents STAT1 nuclear trafficking remains unclear. Herein, we demonstrate that ORF6 directly binds to STAT1 with or without IFN stimulation, resulting in the nuclear exclusion of STAT1. ORF6 also recognizes importin α subtypes with different modes, in particular, high affinity to importin α1 but a low affinity to importin α5. Although ORF6 potentially disrupts the importin α/importin β1-mediated nuclear transport, thereby suppressing the nuclear translocation of the other classical nuclear localization signal-containing cargo proteins, the inhibitory effect of ORF6 is modest when compared with that of STAT1. The results indicate that the drastic nuclear exclusion of STAT1 is attributed to the specific binding with ORF6, which is a distinct strategy for the importin α1-mediated pathway. Combined with the results from a newly-produced replicon system and a hamster model, we conclude that SARS-CoV-2 ORF6 acts as a virulence factor via regulation of nucleocytoplasmic trafficking to accelerate viral replication, resulting in disease progression. - Establishment of a stable SARS-CoV-2 replicon system for application in high-throughput screening
Tomohisa Tanaka; Akatsuki Saito; Tatsuya Suzuki; Yoichi Miyamoto; Kazuo Takayama; Toru Okamoto; Kohji Moriishi
Antiviral Research, 105268, 105268, Elsevier BV, Mar. 2022, [Peer-reviewed], [Last author, Corresponding author]
Scientific journal - Establishment of monoclonal antibodies broadly neutralize infection of hepatitis B virus
Zhang H; Itoh Y; Suzuki T; Ihara KI; Tanaka T; Haga S; Enatsu H; Yumiya M; Kimura M; Takada A; Itoh D; Shibazaki Y; Nakao S; Yoshio S; Miyakawa K; Miyamoto Y; Sasaki H; Kajita T; Sugiyama M; Mizokami M; Tachibana T; Ryo A; Moriishi K; Miyoshi E; Kanto T; Okamoto T; Matsuura Y
MICROBIOLOGY AND IMMUNOLOGY, 66, 4, 179, 192, Wiley, 27 Jan. 2022, [Peer-reviewed], [Invited], [International Magazine]
English, Scientific journal, Antibodies against hepatitis B virus S protein can protect against hepatitis B virus (HBV) infection. Therefore, hepatitis B immunoglobulin (HBIG), which contains HBsAb, is used clinically as a therapy for HBV infection. In this study, a series of monoclonal antibodies that recognize multiple HBV genotypes was obtained. All the antibodies recognized conformational epitopes of S protein, but not linear epitopes. Several antibodies neutralized HBV infection and exhibited strong affinities and neutralizing activities. Antigenic epitope analysis demonstrated that they recognized residue Ile152 of S protein, which is localized outside the "a" determinant. Ile152 is highly conserved, and a mutation in this residue resulted in reduced expression of large hepatitis B surface proteins (L protein), suggesting that the amino acid at this position is involved in the expression of L protein. In addition, the antibodies neutralized the infection of hepatitis D virus possessing a Gly145 mutation to Arg in S protein, which is a well-known escape mutation against HBIG treatment. Using mouse monoclonal antibodies, a humanized antibody possessing affinities and neutralizing activities similar to those of the original mouse antibody was successfully established. The antibodies generated in this study may have the potential for use in alternative antibody therapies for HBV infection. - Inhibitory effect of a novel thiazolidinedione derivative on hepatitis B virus entry.
Tomohisa Tanaka; Kaori Okuyama-Dobashi; Ryoji Motohashi; Hiromasa Yokoe; Kazunori Takahashi; Pattama Wiriyasermkul; Hirotake Kasai; Atsuya Yamashita; Shinya Maekawa; Nobuyuki Enomoto; Akihide Ryo; Shushi Nagamori; Masayoshi Tsubuki; Kohji Moriishi
Antiviral research, 194, 105165, 105165, 19 Aug. 2021, [Peer-reviewed], [Last author, Corresponding author], [International Magazine]
English, Scientific journal, The development of novel antivirals to treat hepatitis B virus (HBV) infection is still needed because currently available drugs do not completely eradicate chronic HBV in some patients. Recently, troglitazone and ciglitazone, classified among the compounds including the thiazolidinedione (TZD) moiety, were found to inhibit HBV infection, but these compounds are not clinically available. In this study, we synthesized 11 TZD derivatives, compounds 1-11, and examined the effect of each compound on HBV infection in HepG2 cells expressing NTCP (HepG2/NTCP cells). Among the derivatives, (Z)-5-((4'-(naphthalen-1-yl)-[1,1'-biphenyl]-4-yl)methylene)thiazolidine-2,4-dione (compound 6) showed the highest antiviral activity, with an IC50 value of 0.3 μM and a selectivity index (SI) of 85, but compound 6 did not affect HCV infection. Treatment with compound 6 inhibited HBV infection in primary human hepatocytes (PHHs) but did not inhibit viral replication in HepG2.2.15 cells or HBV DNA-transfected Huh7 cells. Moreover, treatment with compound 6 significantly impaired hepatitis delta virus (HDV) infection and inhibited a step in HBV particle internalization but did not inhibit attachment of the preS1 lipopeptide or viral particles to the cell surface. These findings suggest that compound 6 interferes with HBV infection via inhibition of the internalization process., 32754909;12393456;12393454;32755008 - Amino Acid Polymorphism in Hepatitis B Virus Associated With Functional Cure.
Takashi Honda; Norie Yamada; Asako Murayama; Masaaki Shiina; Hussein Hassan Aly; Asuka Kato; Takanori Ito; Yoji Ishizu; Teiji Kuzuya; Masatoshi Ishigami; Yoshiki Murakami; Tomohisa Tanaka; Kohji Moriishi; Hironori Nishitsuji; Kunitada Shimotohno; Tetsuya Ishikawa; Mitsuhiro Fujishiro; Masamichi Muramatsu; Takaji Wakita; Takanobu Kato
Cellular and molecular gastroenterology and hepatology, 12, 5, 1583, 1598, 02 Aug. 2021, [Peer-reviewed], [International Magazine]
English, Scientific journal, BACKGROUND & AIMS: To provide an adequate treatment strategy for chronic hepatitis B, it is essential to know which patients are expected to have a good prognosis and which patients do not require therapeutic intervention. Previously, we identified the substitution of isoleucine to leucine at amino acid 97 (I97L) in the hepatitis B core region as a key predictor among patients with stable hepatitis. In this study, we attempted to identify the point at which I97L affects the hepatitis B virus (HBV) life cycle and to elucidate the underlying mechanisms governing the stabilization of hepatitis. METHODS: To confirm the clinical features of I97L, we used a cohort of hepatitis B e antigen-negative patients with chronic hepatitis B infected with HBV-I97 wild-type (wt) or HBV-I97L. The effects of I97L on viral characteristics were evaluated by in vitro HBV production and infection systems with the HBV reporter virus and cell culture-generated HBV. RESULTS: The ratios of reduction in hepatitis B surface antigen and HBV DNA were higher in patients with HBV-I97L than in those with HBV-I97wt. HBV-I97L exhibited lower infectivity than HBV-I97wt in both infection systems with reporter HBV and cell culture-generated HBV. HBV-I97L virions exhibiting low infectivity primarily contained a single-stranded HBV genome. The lower efficiency of cccDNA synthesis was demonstrated after infection of HBV-I97L or transfection of the molecular clone of HBV-I97L. CONCLUSIONS: The I97L substitution reduces the level of cccDNA through the generation of immature virions with single-stranded genomes. This I97L-associated low efficiency of cccDNA synthesis may be involved in the stabilization of hepatitis., 32754985;12393457 - DsRNA Sequencing for RNA Virus Surveillance Using Human Clinical Samples.
Takuma Izumi; Yuhei Morioka; Syun-Ichi Urayama; Daisuke Motooka; Tomokazu Tamura; Takahiro Kawagishi; Yuta Kanai; Takeshi Kobayashi; Chikako Ono; Akinari Morinaga; Takahiro Tomiyama; Norifumi Iseda; Yukiko Kosai; Shoichi Inokuchi; Shota Nakamura; Tomohisa Tanaka; Kohji Moriishi; Hiroaki Kariwa; Tomoharu Yoshizumi; Masaki Mori; Yoshiharu Matsuura; Takasuke Fukuhara
Viruses, 13, 7, 06 Jul. 2021, [Peer-reviewed], [International Magazine]
English, Scientific journal, Although viruses infect various organs and are associated with diseases, there may be many unidentified pathogenic viruses. The recent development of next-generation sequencing technologies has facilitated the establishment of an environmental viral metagenomic approach targeting the intracellular viral genome. However, an efficient method for the detection of a viral genome derived from an RNA virus in animal or human samples has not been established. Here, we established a method for the efficient detection of RNA viruses in human clinical samples. We then tested the efficiency of the method compared to other conventional methods by using tissue samples collected from 57 recipients of living donor liver transplantations performed between June 2017 and February 2019 at Kyushu University Hospital. The viral read ratio in human clinical samples was higher by the new method than by the other conventional methods. In addition, the new method correctly identified viral RNA from liver tissues infected with hepatitis C virus. This new technique will be an effective tool for intracellular RNA virus surveillance in human clinical samples and may be useful for the detection of new RNA viruses associated with diseases. - Hepatitis C virus modulates signal peptide peptidase to alter host protein processing
Junki Hirano; Sachiyo Yoshio; Yusuke Sakai; Li Songling; Tatsuya Suzuki; Yumi Itoh; He Zhang; David Virya Chen; Saori Haga; Hiroko Oomori; Takahiro Kodama; Yusuke Maeda; Yoshihiro Ono; Yu Takahashi; Daron M. Standley; Masahiro Yamamoto; Kohji Moriishi; Kyoji Moriya; Tatsuya Kanto; Tetsuo Takehara; Kazuhiko Koike; Yoshiharu Matsuura; Toru Okamoto
Proceedings of the National Academy of Sciences, 118, 22, e2026184118, e2026184118, Proceedings of the National Academy of Sciences, 01 Jun. 2021, [Peer-reviewed], [International Magazine]
English, Scientific journal, Immunoevasins are viral proteins that prevent antigen presentation on major histocompatibility complex (MHC) class I, thus evading host immune recognition. Hepatitis C virus (HCV) evades immune surveillance to induce chronic infection; however, how HCV-infected hepatocytes affect immune cells and evade immune recognition remains unclear. Herein, we demonstrate that HCV core protein functions as an immunoevasin. Its expression interfered with the maturation of MHC class I molecules catalyzed by the signal peptide peptidase (SPP) and induced their degradation via HMG-CoA reductase degradation 1 homolog, thereby impairing antigen presentation to CD8+ T cells. The expression of MHC class I in the livers of HCV core transgenic mice and chronic hepatitis C patients was impaired but was restored in patients achieving sustained virological response. Finally, we show that the human cytomegalovirus US2 protein, possessing a transmembrane region structurally similar to the HCV core protein, targets SPP to impair MHC class I molecule expression. Thus, SPP represents a potential target for the impairment of MHC class I molecules by DNA and RNA viruses. - Establishment of a Cell Culture Model Permissive for Infection by Hepatitis B and C Viruses
Teruhime Otoguro; Tomohisa Tanaka; Hirotake Kasai; Nobuhiro Kobayashi; Atsuya Yamashita; Takasuke Fukuhara; Akihide Ryo; Moto Fukai; Akinobu Taketomi; Yoshiharu Matsuura; Kohji Moriishi
Hepatology Communications, 5, 4, 634, 649, Wiley, Apr. 2021, [Peer-reviewed], [Last author, Corresponding author]
Scientific journal, 32754909;12393454;12393456;12393459 - Induction of HOX Genes by Hepatitis C Virus Infection via Impairment of Histone H2A Monoubiquitination.
Hirotake Kasai; Kazuki Mochizuki; Tomohisa Tanaka; Atsuya Yamashita; Yoshiharu Matsuura; Kohji Moriishi
Journal of Virology, 95, 6, e01784-20, 24 Feb. 2021, [Peer-reviewed], [Last author, Corresponding author], [International Magazine]
English, Scientific journal, Hepatitis C virus (HCV) infection causes liver pathologies, including hepatocellular carcinoma (HCC). Homeobox (HOX) gene products regulate embryonic development and are associated with tumorigenesis, although the regulation of HOX genes by HCV infection has not been clarified in detail. We examined the effect of HCV infection on HOX gene expression. In this study, HCV infection induced more than half of the HOX genes and reduced the level of histone H2A monoubiquitination on lysine 119 (K119) (H2Aub), which represses HOX gene promoter activity. HCV infection also promoted proteasome-dependent degradation of RNF2, which is an E3 ligase mediating H2A monoubiquitination as a component of polycomb repressive complex 1. Since full-genomic replicon cells but not subgenomic replicon cells exhibited reduced RNF2 and H2Aub levels and induction of HOX genes, we focused on the core protein. Expression of the core protein reduced the amounts of RNF2 and H2Aub and induced HOX genes. Treatment with LY-411575, which can reduce HCV core protein expression via signal peptide peptidase (SPP) inhibition without affecting other viral proteins, dose-dependently restored the amounts of RNF2 and H2Aub in HCV-infected cells and impaired the induction of HOX genes and production of viral particles but not viral replication. The chromatin immunoprecipitation assay results also indicated infection- and proteasome-dependent reductions in H2Aub located in HOX gene promoters. These results suggest that HCV infection or core protein induces HOX genes by impairing histone H2A monoubiquitination via a reduction in the RNF2 level.IMPORTANCE Recently sustained virologic response can be achieved by direct-acting antiviral (DAA) therapy in most hepatitis C patients. Unfortunately, DAA therapy does not completely eliminate a risk of hepatocellular carcinoma (HCC). Several epigenetic factors, including histone modifications, are well known to contribute to hepatitis C virus (HCV)-associated HCC. However, the regulation of histone modifications by HCV infection has not been clarified in detail. In this study, our data suggest that HCV infection or HCV core protein expression impairs monoubiquitination of histone H2A K119 in the homeobox (HOX) gene promoter via destabilization of RNF2 and then induces HOX genes. Several lines of evidence suggest that the expression of several HOX genes is dysregulated in certain types of tumors. These findings reveal a novel mechanism of HCV-related histone modification and may provide information about new targets for diagnosis and prevention of HCC occurrence., 32754909;12393454;12393456;12393457 - Deep Sequencing Analysis of Serum Hepatitis B Virus-RNA During Nucleot (side Analogue Therapy
Matsuda, S; Maekawa, S; Komiyama, Y; Nakakuki, N; Muraoka, M; Suzuki, Y; Sato, M; Tatsumi, A; Miura, M; Amemiya, F; Shindo, H; Takano, S; Fukasawa, M; Yamaguchi, T; Nakayama, Y; Inoue, T; Sato, T; Yamashita, A; Moriishi, K; Enomoto, N
HEPATOLOGY RESEARCH, 51, 1, 39, 50, Wiley, 22 Jan. 2021, [Peer-reviewed]
English, Scientific journal - Establishment of a novel hepatitis B virus culture system using immortalized human hepatocytes.
Yuichi Akahori; Hiroki Kato; Takashi Fujita; Kohji Moriishi; Yasuhito Tanaka; Koichi Watashi; Michio Imamura; Kazuaki Chayama; Takaji Wakita; Makoto Hijikata
Scientific reports, 10, 1, 21718, 21718, 10 Dec. 2020, [Peer-reviewed], [International Magazine]
English, Scientific journal, Recent development of hepatitis B virus (HBV) culture systems has made it possible to analyze the almost all steps of the viral life cycle. However, the reproducibility of interaction between HBV and host cells seemed inaccurate in those systems because of utilization of cancer cell lines with a difference from hepatocytes in the majority of cases. In this study, in order to resolve this point, a novel HBV culture system using non-cancer-derived immortalized human hepatocytes derived cell lines, producing exogenous human sodium taurocholate cotransporting polypeptide, was developed. One of the cell clones, E/NtG8 cells, was permissive to both blood-borne HBV (HBVbb) and culture-derived recombinant HBV when cultured in the three-dimensional condition. Furthermore, the production of infectious HBV particles, which showed the similar physicochemical properties to HBVbb, was observed for about a month after HBVbb infection in this system, suggesting that it may reproduce whole steps of the HBV lifecycle under the condition analogous to human liver cells infected with HBV. This system seemed to contribute not only to find novel interactions between HBV and host cells but also to understand mechanism of HBV pathogenesis. - Identification of Two Critical Neutralizing Epitopes in the Receptor Binding Domain of Hepatitis B Virus preS1.
Keigo Yato; Taishi Onodera; Mami Matsuda; Saya Moriyama; Akira Fujimoto; Koichi Watashi; Hideki Aizaki; Tomohisa Tanaka; Kohji Moriishi; Hironori Nishitsuji; Kunitada Shimotohno; Koji Tamura; Yoshimasa Takahashi; Takaji Wakita; Masamichi Muramatsu; Takanobu Kato; Ryosuke Suzuki
Journal of virology, 09 Dec. 2020, [Peer-reviewed], [International Magazine]
English, Scientific journal, Hepatitis B virus (HBV) infection is a major public health problem. Human hepatocytes are infected with HBV via binding between the preS1 region in the large envelope protein of HBV and sodium taurocholate cotransporting polypeptide. Although several monoclonal antibodies (MAbs) that recognize the receptor binding domain in preS1 and neutralize HBV infection have been isolated, details of neutralizing epitopes are not understood. In this study, we generated 13 MAbs targeting the preS1 receptor binding domain from preS1-specific memory B cells derived from DNA immunized mice. The MAbs were classified into three groups according to the epitope regions, designated epitopes I-III. A virus neutralization assay revealed that MAbs recognizing epitopes I and III neutralized HBV infection, suggesting that these domains are critical epitopes for viral neutralization. In addition, a neutralization assay against multiple genotypes of HBV revealed that epitope I is a semi-pangenotypic neutralizing epitope, whereas epitope III is a genotype-specific epitope. We also showed that neutralizing MAbs against preS1 could neutralize HBV bearing vaccine-induced escape mutation. These findings provide insight into novel immunoprophylaxis for the prevention and treatment of HBV infection.IMPORTANCE The HBV preS1 2-47 aa region (preS1/2-47) is essential for virus binding with sodium taurocholate cotransporting polypeptide. Several MAbs targeting preS1/2-47 have been reported to neutralize HBV infection; however, which region in preS1/2-47 contains the critical neutralizing epitope for HBV infection is unclear. Here, we generated several MAbs targeting preS1/2-47 and found that MAbs recognizing the N- or C-terminus of preS1/2-47 remarkably neutralized HBV infection. We further confirmed the neutralizing activity of anti-preS1 MAbs against HBV with vaccine escape mutation. These data clarified the relationship between the antibody epitope and the virus neutralizing activity and also suggested the potential ability of a vaccine antigen containing the preS1 region to overcome the weakness of current HB vaccines comprising the small S protein. - Cancer-related genetic changes in multistep hepatocarcinogenesis and their correlation with imaging and histological findings
Muraoka, M; Maekawa, S; Suzuki, Y; Sato, M; Tatsumi, A; Matsuda, S; Miura, M; Nakakuki, N; Shindo, H; Amemiya, F; Takano, S; Fukasawa, M; Nakayama, Y; Yamaguchi, T; Inoue, T; Sato, T; Yamashita, A; Moriishi, K; Matsuda, M; Enomoto, N
HEPATOLOGY RESEARCH, 50, 9, 1071, 1081, Wiley, Sep. 2020, [Peer-reviewed]
English, Scientific journal - N-terminal PreS1 Sequence Regulates Efficient Infection of Cell Culture-generated Hepatitis B Virus.
Asako Murayama; Norie Yamada; Yoshiki Osaki; Masaaki Shiina; Hussein Hassan Aly; Masashi Iwamoto; Senko Tsukuda; Koichi Watashi; Mami Matsuda; Ryosuke Suzuki; Tomohisa Tanaka; Kohji Moriishi; Tetsuro Suzuki; Hironori Nishitsuji; Masaya Sugiyama; Masashi Mizokami; Kunitada Shimotohno; Takaji Wakita; Masamichi Muramatsu; T Jake Liang; Takanobu Kato
Hepatology (Baltimore, Md.), 73, 2, 520, 532, 23 May 2020, [Peer-reviewed], [International Magazine]
English, Scientific journal, BACKGROUND & AIMS: An efficient cell culture system for hepatitis B virus (HBV) is indispensable for research on viral characteristics and anti-viral reagents. Currently, for the HBV infection assay in cell culture, viruses derived from HBV genome-integrated cell lines of HepG2.2.15 or HepAD-38 are commonly used. However, these viruses are not suitable for the evaluation of polymorphism dependent-viral characteristics or resistant mutations against anti-viral reagents. HBV obtained by the transient transfection of the ordinary HBV molecular clone has limited infection efficiencies in cell culture. APPROACH & RESULTS: We found that an 11 amino acid deletion (d11) in the preS1 region enhances the infectivity of cell culture-generated HBV (HBVcc) to sodium taurocholate co-transporting polypeptide-transduced HepG2 (HepG2/NTCP) cells. Infection of HBVcc derived from a d11-introduced genotype C strain (GTC-d11) was approximately 10-fold more efficient than infection of wild-type GTC (GTC-wt), and the number of infected cells was comparable between GTC-d11- and HepG2.2.15-derived viruses when inoculated with the same genome equivalents. A time-dependent increase in pre-genomic RNA and efficient synthesis of covalently closed circular DNA were detected after infection with the GTC-d11 virus. The involvement of d11 in the L-HBs protein in the enhanced infectivity was confirmed by an HBV reporter virus and hepatitis D virus infection system. The binding step of the GTC-d11 virus onto the cell surface was responsible for this efficient infection. CONCLUSIONS: This system provides a powerful tool for studying the infection and propagation of HBV in cell culture, and also for developing the anti-viral strategy against HBV infection. - Anti‐viral effects of interferon‐λ3 on hepatitis B virus infection in cell culture
Norie Yamada; Asako Murayama; Masaaki Shiina; Hussein Hassan Aly; Masashi Iwamoto; Senko Tsukuda; Koichi Watashi; Tomohisa Tanaka; Kohji Moriishi; Hironori Nishitsuji; Masaya Sugiyama; Masashi Mizokami; Kunitada Shimotohno; Masamichi Muramatsu; Kazumoto Murata; Takanobu Kato
Hepatology Research, 50, 3, 283, 291, Wiley, Mar. 2020, [Peer-reviewed], [International Magazine]
English, Scientific journal, AIM: Interferon (IFN)-λ3 is known to have antiviral effects against various pathogens. Recently, it has been reported that the production of IFN-λ3 in colon cells after the administration of nucleotide analogs is expected to reduce hepatitis B surface antigen in chronic hepatitis B patients. Here, we aimed to prove the antiviral effects of IFN-λ3 on hepatitis B virus (HBV) by using an in vitro HBV production and infection system. METHODS: We used HepG2.2.15-derived HBV as an inoculum and the replication-competent molecular clone of HBV as a replication model. RESULTS: By administering IFN-λ3 to HepG2 cells transfected with the HBV molecular clone, the production of hepatitis B surface antigen and hepatitis B core-related antigen was reduced dose-dependently. IFN-λ3 treatment also reduced the number of HBV-positive cells and the synthesis of covalently closed circular DNA after infection of HepG2.2.15-derived HBV to sodium taurocholate cotransporting polypeptide-transduced HepG2 cells. The inhibitory effect on HBV infection by IFN-λ3 was confirmed by using a recombinant a HBV reporter virus system. To elucidate the underlying mechanisms of the anti-HBV effect of IFN-λ3, we assessed the transcription of HBV RNA and the production of core-associated HBV DNA in HBV molecular clone-transfected HepG2 cells, and found that both parameters were reduced by IFN-λ3. CONCLUSIONS: We observed that the administration of IFN-λ3 inhibits HBV infection and the production of HBV proteins at the HBV RNA transcription level. This finding provides novel insight into the treatment of chronic hepatitis B patients with the administration or induction of IFN-λ3. - C-terminal α Domain of p63 Binds to p300 to Coactivate β-Catenin.
Katoh I; Maehata Y; Moriishi K; Hata RI; Kurata SI
Neoplasia (New York, N.Y.), 21, 5, 494, 503, May 2019, [Peer-reviewed] - USP15 Participates in Hepatitis C Virus Propagation through Regulation of Viral RNA Translation and Lipid Droplet Formation.
Shinji Kusakabe; Tatsuya Suzuki; Yukari Sugiyama; Saori Haga; Kanako Horike; Makoto Tokunaga; Junki Hirano; He Zhang; David Virya Chen; Hanako Ishiga; Yasumasa Komoda; Chikako Ono; Takasuke Fukuhara; Masahiro Yamamoto; Masahito Ikawa; Takashi Satoh; Shizuo Akira; Tomohisa Tanaka; Kohji Moriishi; Moto Fukai; Akinobu Taketomi; Sachiyo Yoshio; Tatsuya Kanto; Tetsuro Suzuki; Toru Okamoto; Yoshiharu Matsuura
Journal of virology, 93, 6, 15 Mar. 2019, [Peer-reviewed], [International Magazine]
English, Scientific journal, Hepatitis C virus (HCV) utilizes cellular factors for efficient propagation. Ubiquitin is covalently conjugated to the substrate to alter its stability or to modulate signal transduction. In this study, we examined the importance of ubiquitination for HCV propagation. We found that inhibition of deubiquitinating enzymes (DUBs) or overexpression of nonspecific DUBs impaired HCV replication, suggesting that ubiquitination regulates HCV replication. To identify specific DUBs involved in HCV propagation, we set up RNA interference (RNAi) screening against DUBs and successfully identified ubiquitin-specific protease 15 (USP15) as a novel host factor for HCV propagation. Our studies showed that USP15 is involved in translation of HCV RNA and production of infectious HCV particles. In addition, deficiency of USP15 in human hepatic cell lines (Huh7 and Hep3B/miR-122 cells) but not in a nonhepatic cell line (293T cells) impaired HCV propagation, suggesting that USP15 participates in HCV propagation through the regulation of hepatocyte-specific functions. Moreover, we showed that loss of USP15 had no effect on innate immune responses in vitro and in vivo We also found that USP15-deficient Huh7 cells showed reductions in the amounts of lipid droplets (LDs), and the addition of palmitic acids restored the production of infectious HCV particles. Taken together, these data suggest that USP15 participates in HCV propagation by regulating the translation of HCV RNA and the formation of LDs.IMPORTANCE Although ubiquitination has been shown to play important roles in the HCV life cycle, the roles of deubiquitinating enzymes (DUBs), which cleave ubiquitin chains from their substrates, in HCV propagation have not been investigated. Here, we identified USP15 as a DUB regulating HCV propagation. USP15 showed no interaction with viral proteins and no participation in innate immune responses. Deficiency of USP15 in Huh7 cells resulted in suppression of the translation of HCV RNA and reduction in the amounts of lipid droplets, and the addition of fatty acids partially restored the production of infectious HCV particles. These data suggest that USP15 participates in HCV propagation in hepatic cells through the regulation of viral RNA translation and lipid metabolism. - Potential Risk of Virus Carryover by Fabrics of Personal Protective Gowns.
Katoh I; Tanabe F; Kasai H; Moriishi K; Shimasaki N; Shinohara K; Uchida Y; Koshiba T; Arakawa S; Morimoto M
Frontiers in public health, 7, 121, 2019, [Peer-reviewed] - HBV preS deletion mapping using deep sequencing demonstrates a unique association with viral markers.
Suzuki Y; Maekawa S; Komatsu N; Sato M; Tatsumi A; Miura M; Matsuda S; Muraoka M; Nakakuki N; Amemiya F; Takano S; Fukasawa M; Nakayama Y; Yamaguchi T; Inoue T; Sato T; Sakamoto M; Yamashita A; Moriishi K; Enomoto N
PloS one, 14, 2, e0212559, e0212559, Public Library of Science (PLoS), 2019, [Peer-reviewed]
Scientific journal - HBV patients with low HBsAg and high HBcrAg titers have a high risk of HBV-related HCC.
Suzuki Y; Maekawa S; Komatsu N; Sato M; Tatsumi A; Miura M; Matsuda S; Muraoka M; Nakakuki N; Shindo H; Amemiya F; Takano S; Fukasawa M; Nakayama Y; Yamaguchi T; Inoue T; Sato T; Sakamoto M; Yamashita A; Moriishi K; Enomoto N
Hepatology research : the official journal of the Japan Society of Hepatology, 49, 1, 51, 63, Wiley, Oct. 2018, [Peer-reviewed]
Scientific journal - Roles of the 5' untranslated region of nonprimate hepacivirus in translation initiation and viral replication
Tomohisa Tanaka; Teruhime Otoguro; Atsuya Yamashita; Hirotake Kasai; Takasuke Fukuhara; Yoshiharu Matsuura; Kohji Moriishi
Journal of Virology, 92, 7, American Society for Microbiology, 01 Apr. 2018, [Peer-reviewed], [Last author, Corresponding author]
English, Scientific journal - Seroepidemiology of non-primate hepacivirus (NPHV) in Japanese native horses
Shizuka HAYASHI; Tomohisa TANAKA; Kohji MORIISHI; Kazuhiro HIRAYAMA; Akio YAMADA; Kozue HOTTA
Journal of Veterinary Medical Science, 80, 1, 186, 189, Japanese Society of Veterinary Science, 2018, [Peer-reviewed]
Scientific journal - Catechol Group of Cinnamic Acid Derivative Is Essential for Its Anti-Hepatitis C Virus Activity.
Amano R; Yamashita A; Kasai H; Hori T; Miyasato S; Saito S; Tsubuki M; Moriishi K
Yamanashi Medical Journal, 32, 2, 95, 103, Jan. 2018, [Peer-reviewed], [Last author, Corresponding author]
English, Scientific journal - Seroepidemiology of non-primate hepacivirus (NPHV) in Japanese native horses
Shizuka HAYASHI; Tomohisa TANAKA; Kohji MORIISHI; Kazuhiro HIRAYAMA; Akio YAMADA; Kozue HOTTA
Journal of Veterinary Medical Science, 80, 1, 186, 189, Japanese Society of Veterinary Science, 2018, [Peer-reviewed], [Domestic magazines]
English, Scientific journal - Characterization of SPP inhibitors suppressing propagation of HCV and protozoa
Junki Hirano; Toru Okamoto; Yukari Sugiyama; Tatsuya Suzuki; Shinji Kusakabe; Makoto Tokunaga; Takasuke Fukuhara; Miwa Sasai; Takahiro Tougan; Yasue Matsunaga; Kazuo Yamashita; Yusuke Sakai; Masahiro Yamamoto; Toshihiro Horii; Daron M. Standley; Kohji Moriishi; Kyoji Moriya; Kazuhiko Koike; Yoshiharu Matsuura
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 114, 50, E10782, E10791, Dec. 2017, [Peer-reviewed]
English, Scientific journal - Insights into the mechanism of isoenzyme-specific signal peptide peptidase-mediated translocation of heme oxygenase
Bianca Schaefer; Kohji Moriishi; Soenke Behrends
PLOS ONE, 12, 11, e0188344, Nov. 2017, [Peer-reviewed]
English, Scientific journal - Cinnamic acid derivatives inhibit hepatitis C virus replication via the induction of oxidative stress
Ryota Amano; Atsuya Yamashita; Hirotake Kasai; Tomoka Hori; Sayoko Miyasato; Setsu Saito; Hiromasa Yokoe; Kazunori Takahashi; Tomohisa Tanaka; Teruhime Otoguro; Shinya Maekawa; Nobuyuki Enomoto; Masayoshi Tsubuki; Kohji Moriishi
ANTIVIRAL RESEARCH, 145, 123, 130, Sep. 2017, [Peer-reviewed], [Last author, Corresponding author]
English, Scientific journal - Inhibitory effects of metachromin A on hepatitis B virus production via impairment of the viral promoter activity
Atsuya Yamashita; Mayumi Tamaki; Hirotake Kasai; Tomohisa Tanaka; Teruhime Otoguro; Akihide Ryo; Shinya Maekawa; Nobuyuki Enomoto; Nicole J. de Voogd; Junichi Tanaka; Kohji Moriishi
ANTIVIRAL RESEARCH, 145, 136, 145, Sep. 2017, [Peer-reviewed], [Last author, Corresponding author]
English, Scientific journal - Immunological function of Langerhans cells in HIV infection
Takamitsu Matsuzawa; Youichi Ogawa; Kohji Moriishi; Shinji Shimada; Tatsuyoshi Kawamura
JOURNAL OF DERMATOLOGICAL SCIENCE, 87, 2, 159, 167, Aug. 2017, [Peer-reviewed]
English, Scientific journal - Hepatitis B virus prevents excessive viral production via reduction of cell death-inducing DFF45-like effectors
Jun Yasumoto; Hirotake Kasai; Kentaro Yoshimura; Teruhime Otoguro; Koichi Watashi; Takaji Wakita; Atsuya Yamashita; Tomohisa Tanaka; Sen Takeda; Kohji Moriishi
JOURNAL OF GENERAL VIROLOGY, 98, 7, 1762, 1773, Jul. 2017, [Peer-reviewed], [Last author, Corresponding author]
English, Scientific journal - Four Aromatic Sulfates with an Inhibitory Effect against HCV NS3 Helicase from the Crinoid Alloeocomatella polycladia
Idam Hermawan; Atsushi Furuta; Masahiro Higashi; Yoshihisa Fujita; Nobuyoshi Akimitsu; Atsuya Yamashita; Kohji Moriishi; Satoshi Tsuneda; Hidenori Tani; Masamichi Nakakoshi; Masayoshi Tsubuki; Yuji Sekiguchi; Naohiro Noda; Junichi Tanaka
MARINE DRUGS, 15, 4, Apr. 2017, [Peer-reviewed]
English, Scientific journal - The potential of signal peptide peptidase as a therapeutic target for hepatitis C
Kohji Moriishi
EXPERT OPINION ON THERAPEUTIC TARGETS, 21, 9, 827, 836, 2017, [Peer-reviewed], [Lead author, Last author, Corresponding author]
English - Inhibitory effect of presenilin inhibitor LY411575 on maturation of hepatitis C virus core protein, production of the viral particle and expression of host proteins involved in pathogenicity
Teruhime Otoguro; Tomohisa Tanaka; Hirotake Kasai; Atsuya Yamashita; Kohji Moriishi
MICROBIOLOGY AND IMMUNOLOGY, 60, 11, 740, 753, Nov. 2016, [Peer-reviewed], [Last author, Corresponding author]
English, Scientific journal - Single peptide peptidase a target for anti-HCV drug
Toru Okamoto; Junki Hirano; Tatsuya Suzuki; Shinji Kusakabe; Takasuke Fukuhara; Kohji Moriishi; Kazuhiko Koike; Yoshiharu Matsuura
Oct. 2016, [Peer-reviewed]
English, Research society - Inhibitory effect of CDK9 inhibitor FIT-039 on hepatitis B virus propagation
Tomohisa Tanaka; Kaori Okuyama-Dobashi; Shuko Murakami; Wenjia Chen; Toru Okamoto; Keiji Ueda; Takamitsu Hosoya; Yoshiharu Matsuura; Akihide Ryo; Yasuhito Tanaka; Masatoshi Hagiwara; Kohji Moriishi
ANTIVIRAL RESEARCH, 133, 156, 164, Sep. 2016, [Peer-reviewed], [Last author, Corresponding author]
English, Scientific journal - The Alarmin IL-33 Derived from HSV-2-Infected Keratinocytes Triggers Mast Cell-Mediated Antiviral Innate Immunity
Rui Aoki; Tatsuyoshi Kawamura; Fumi Goshima; Youichi Ogawa; Susumu Nakae; Kohji Moriishi; Atsuhito Nakao; Shinji Shimada
JOURNAL OF INVESTIGATIVE DERMATOLOGY, 136, 6, 1290, 1292, Jun. 2016, [Peer-reviewed]
English - TRC8-dependent degradation of hepatitis C virus immature core protein regulates viral propagation and pathogenesis
Sayaka Aizawa; Toru Okamoto; Yukari Sugiyama; Takahisa Kouwaki; Ayano Ito; Tatsuya Suzuki; Chikako Ono; Takasuke Fukuhara; Masahiro Yamamoto; Masayasu Okochi; Nobuhiko Hiraga; Michio Imamura; Kazuaki Chayama; Ryosuke Suzuki; Ikuo Shoji; Kohji Moriishi; Kyoji Moriya; Kazuhiko Koike; Yoshiharu Matsuura
NATURE COMMUNICATIONS, 7, 11379, May 2016, [Peer-reviewed]
English, Scientific journal - Hepatocyte Factor JMJD5 Regulates Hepatitis B Virus Replication through Interaction with HBx
Takahisa Kouwaki; Toru Okamoto; Ayano Ito; Yukari Sugiyama; Kazuo Yamashita; Tatsuya Suzuki; Shinji Kusakabe; Junki Hirano; Takasuke Fukuhara; Atsuya Yamashita; Kazunobu Saito; Daisuke Okuzaki; Koichi Watashi; Masaya Sugiyama; Sachiyo Yoshio; Daron M. Standley; Tatsuya Kanto; Masashi Mizokami; Kohji Moriishi; Yoshiharu Matsuura
JOURNAL OF VIROLOGY, 90, 7, 3530, 3542, Apr. 2016, [Peer-reviewed]
English, Scientific journal - Repression of Wnt/beta-catenin response elements by p63 (TP63)
Iyoko Katoh; Nahoko Fukunishi; Masahiro Fujimuro; Hirotake Kasai; Kohji Moriishi; Ryu-Ichiro Hata; Shun-ichi Kurata
CELL CYCLE, 15, 5, 699, 710, Mar. 2016, [Peer-reviewed]
English, Scientific journal - Structural proteins of HCV and biological functions
Kohji Moriishi; Yoshiharu Matsuura
Hepatitis C Virus I: Cellular and Molecular Virology, 105, 127, Springer Japan, 01 Jan. 2016, [Peer-reviewed], [Lead author, Corresponding author]
English, In book - Identification of Antiviral Agents Targeting Hepatitis B Virus Promoter from Extracts of Indonesian Marine Organisms by a Novel Cell-Based Screening Assay
Atsuya Yamashita; Yuusuke Fujimoto; Mayumi Tamaki; Andi Setiawan; Tomohisa Tanaka; Kaori Okuyama-Dobashi; Hirotake Kasai; Koichi Watashi; Takaji Wakita; Masaaki Toyama; Masanori Baba; Nicole J. de Voogd; Shinya Maekawa; Nobuyuki Enomoto; Junichi Tanaka; Kohji Moriishi
MARINE DRUGS, 13, 11, 6759, 6773, Nov. 2015, [Peer-reviewed], [Last author, Corresponding author]
English, Scientific journal - Involvement of FKBP6 in hepatitis C virus replication
Hirotake Kasai; Kunihiro Kawakami; Hiromasa Yokoe; Kentaro Yoshimura; Masanori Matsuda; Jun Yasumoto; Shinya Maekawa; Atsuya Yamashita; Tomohisa Tanaka; Masanori Ikeda; Nobuyuki Kato; Toru Okamoto; Yoshiharu Matsuura; Naoya Sakamoto; Nobuyuki Enomoto; Sen Takeda; Hideki Fujii; Masayoshi Tsubuki; Masami Kusunoki; Kohji Moriishi
SCIENTIFIC REPORTS, 5, 16699, Nov. 2015, [Peer-reviewed], [Last author, Corresponding author]
English, Scientific journal - Hepatitis B virus efficiently infects non-adherent hepatoma cells via human sodium taurocholate cotransporting polypeptide
Kaori Okuyama-Dobashi; Hirotake Kasai; Tomohisa Tanaka; Atsuya Yamashita; Jun Yasumoto; Wenjia Chen; Toru Okamoto; Shinya Maekawa; Koichi Watashi; Takaji Wakita; Akihide Ryo; Tetsuro Suzuki; Yoshiharu Matsuura; Nobuyuki Enomoto; Kohji Moriishi
SCIENTIFIC REPORTS, 5, 17047, Nov. 2015, [Peer-reviewed], [Last author, Corresponding author]
English, Scientific journal - TRC8-dependent proteasome degradation of immature core protein participates in pathogenesis of HCV
Toru Okamoto; Yukari Sugiyama; Takahisa Kouwaki; Ayano Ito; Takasuke Fukuhara; Kohji Moriishi; Kazuhiko Koike; Yoshiharu Matusuura
Oct. 2015, [Peer-reviewed]
English, International conference proceedings - Identification of Hydroxyanthraquinones as Novel Inhibitors of Hepatitis C Virus NS3 Helicase
Atsushi Furuta; Masayoshi Tsubuki; Miduki Endoh; Tatsuki Miyamoto; Junichi Tanaka; Kazi Abdus Salam; Nobuyoshi Akimitsu; Hidenori Tani; Atsuya Yamashita; Kohji Moriishi; Masamichi Nakakoshi; Yuji Sekiguchi; Satoshi Tsuneda; Naohiro Noda
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 16, 8, 18439, 18453, Aug. 2015, [Peer-reviewed]
English, Scientific journal - Novel sex-dependent differentially methylated regions are demethylated in adult male mouse livers
Shuhei Ito; Keiji Hirabayashi; Kohji Moriishi; Yasuhisa Matsui; Kyoji Moriya; Kazuhiko Koike; Yoshiharu Matsuura; Kunio Shiota; Shintaro Yagi
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 462, 4, 332, 338, Jul. 2015, [Peer-reviewed]
English, Scientific journal - Deep Sequencing and Phylogenetic Analysis of Variants Resistant to Interferon-Based Protease Inhibitor Therapy in Chronic Hepatitis Induced by Genotype 1b Hepatitis C Virus
Mitsuaki Sato; Shinya Maekawa; Nobutoshi Komatsu; Akihisa Tatsumi; Mika Miura; Masaru Muraoka; Yuichiro Suzuki; Fumitake Amemiya; Shinichi Takano; Mitsuharu Fukasawa; Yasuhiro Nakayama; Tatsuya Yamaguchi; Tomoyoshi Uetake; Taisuke Inoue; Tadashi Sato; Minoru Sakamoto; Atsuya Yamashita; Kohji Moriishi; Nobuyuki Enomotoa
JOURNAL OF VIROLOGY, 89, 11, 6105, 6116, Jun. 2015, [Peer-reviewed]
English, Scientific journal - Long-term imipramine treatment increases N-methyl-D-aspartate receptor activity and expression via epigenetic mechanisms
Nguyen An Nghia; Takae Hirasawa; Hirotake Kasai; Chie Obata; Kohji Moriishi; Kazuki Mochizuki; Schuichi Koizumi; Takeo Kubota
EUROPEAN JOURNAL OF PHARMACOLOGY, 752, 69, 77, Apr. 2015, [Peer-reviewed]
English, Scientific journal - Maternal restraint stress during pregnancy in mice induces 11 beta-HSD1-associated metabolic changes in the livers of the offspring
H. Maeyama; T. Hirasawa; Y. Tahara; C. Obata; H. Kasai; K. Moriishi; K. Mochizuki; T. Kubota
JOURNAL OF DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE, 6, 2, 105, 114, Apr. 2015, [Peer-reviewed]
English, Scientific journal - Hallmarks of Hepatitis C Virus in Equine Hepacivirus
Tomohisa Tanaka; Hirotake Kasai; Atsuya Yamashita; Kaori Okuyama-Dobashi; Jun Yasumoto; Shinya Maekawa; Nobuyuki Enomoto; Toru Okamoto; Yoshiharu Matsuura; Masami Morimatsu; Noboru Manabe; Kazuhiko Ochiai; Kazuto Yamashita; Kohji Moriishi
JOURNAL OF VIROLOGY, 88, 22, 13352, 13366, Nov. 2014, [Peer-reviewed], [Last author, Corresponding author]
English, Scientific journal - Processing of Core Protein by Signal Peptide Peptidase Participates in Propagation and Pathogenesis of Hepatitis C Virus
Toru Okamoto; Sayaka Aizawa; Takahisa Kouwaki; Tatsuya Suzuki; Francesc Puig-Basagoiti; Shinya Watanabe; Takasuke Fukuhara; Kohji Moriishi; Kazuhiko Koike; Yoshiharu Matsuura
Sep. 2014, [Peer-reviewed]
English, International conference proceedings - Cholesterol sulfate as a potential inhibitor of hepatitis C virus NS3 helicase
Atsushi Furuta; Kazi Abdus Salam; Nobuyoshi Akimitsu; Junichi Tanaka; Hidenori Tani; Atsuya Yamashita; Kohji Moriishi; Masamichi Nakakoshi; Masayoshi Tsubuki; Yuji Sekiguchi; Satoshi Tsuneda; Naohiro Noda
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY, 29, 2, 223, 229, Apr. 2014, [Peer-reviewed]
English, Scientific journal - EFdA, a Reverse Transcriptase Inhibitor, Potently Blocks HIV-1 Ex Vivo Infection of Langerhans Cells within Epithelium
Takamitsu Matsuzawa; Tatsuyoshi Kawamura; Youichi Ogawa; Kenji Maeda; Hirotomo Nakata; Kohji Moriishi; Yoshio Koyanagi; Hiroyuki Gatanaga; Shinji Shimada; Hiroaki Mitsuya
JOURNAL OF INVESTIGATIVE DERMATOLOGY, 134, 4, 1158, 1161, Apr. 2014, [Peer-reviewed]
English - PBDE: Structure-Activity Studies for the Inhibition of Hepatitis C Virus NS3 Helicase
Kazi Abdus Salam; Atsushi Furuta; Naohiro Noda; Satoshi Tsuneda; Yuji Sekiguchi; Atsuya Yamashita; Kohji Moriishi; Masamichi Nakakoshi; Hidenori Tani; Sona Rani Roy; Junichi Tanaka; Masayoshi Tsubuki; Nobuyoshi Akimitsu
MOLECULES, 19, 4, 4006, 4020, Apr. 2014, [Peer-reviewed]
English, Scientific journal - Identification and Biochemical Characterization of Halisulfate 3 and Suvanine as Novel Inhibitors of Hepatitis C Virus NS3 Helicase from a Marine Sponge
Atsushi Furuta; Kazi Abdus Salam; Idam Hermawan; Nobuyoshi Akimitsu; Junichi Tanaka; Hidenori Tani; Atsuya Yamashita; Kohji Moriishi; Masamichi Nakakoshi; Masayoshi Tsubuki; Poh Wee Peng; Youichi Suzuki; Naoki Yamamoto; Yuji Sekiguchi; Satoshi Tsuneda; Naohiro Noda
MARINE DRUGS, 12, 1, 462, 476, Jan. 2014, [Peer-reviewed]
English, Scientific journal - Binding of HSV-1 Glycoprotein K (gK) to Signal Peptide Peptidase (SPP) Is Required for Virus Infectivity
Sariah J. Allen; Kevin R. Mott; Yoshiharu Matsuura; Kohji Moriishi; Konstantin G. Kousoulas; Homayon Ghiasi
PLOS ONE, 9, 1, e85360, Jan. 2014, [Peer-reviewed]
English, Scientific journal - Oral Administration of the CCR5 Inhibitor, Maraviroc, Blocks HIV Ex Vivo Infection of Langerhans Cells within the Epithelium
Takamitsu Matsuzawa; Tatsuyoshi Kawamura; Youichi Ogawa; Masaaki Takahashi; Rui Aoki; Kohji Moriishi; Yoshio Koyanagi; Hiroyuki Gatanaga; Andrew Blauvelt; Shinji Shimada
JOURNAL OF INVESTIGATIVE DERMATOLOGY, 133, 12, 2803, 2805, Dec. 2013, [Peer-reviewed]
English - Deep-sequencing analysis of the association between the quasispecies nature of the hepatitis C virus core region and disease progression
Mika Miura; Shinya Maekawa; Shinichi Takano; Nobutoshi Komatsu; Akihisa Tatsumi; Yukiko Asakawa; Kuniaki Shindo; Fumitake Amemiya; Yasuhiro Nakayama; Taisuke Inoue; Minoru Sakamoto; Atsuya Yamashita; Kohji Moriishi; Nobuyuki Enomoto
Journal of Virology, 87, 23, 12541, 12551, Dec. 2013, [Peer-reviewed]
English, Scientific journal - Inhibitory Effects of Caffeic Acid Phenethyl Ester Derivatives on Replication of Hepatitis C Virus
Hui Shen; Atsuya Yamashita; Masamichi Nakakoshi; Hiromasa Yokoe; Masashi Sudo; Hirotake Kasai; Tomohisa Tanaka; Yuusuke Fujimoto; Masanori Ikeda; Nobuyuki Kato; Naoya Sakamoto; Hiroko Shindo; Shinya Maekawa; Nobuyuki Enomoto; Masayoshi Tsubuki; Kohji Moriishi
PLOS ONE, 8, 12, e82299, Dec. 2013, [Peer-reviewed], [Last author, Corresponding author]
English, Scientific journal - Psammaplin A inhibits hepatitis C virus NS3 helicase.
Kazi Abdus Salam; Atsushi Furuta; Naohiro Noda; Satoshi Tsuneda; Yuji Sekiguchi; Atsuya Yamashita; Kohji Moriishi; Masamichi Nakakoshi; Masayoshi Tsubuki; Hidenori Tani; Junichi Tanaka; Nobuyoshi Akimitsu
Journal of natural medicines, 67, 4, 765, 72, Oct. 2013, [Peer-reviewed], [Domestic magazines]
English, Hepatitis C virus (HCV) is the causative agent of hepatitis C, a chronic infectious disease that can lead to development of hepatocellular carcinoma. The NS3 nucleoside triphosphatase (NTPase)/helicase has an essential role in HCV replication, and is therefore an attractive target for direct-acting antiviral strategies. In this study, we employed high-throughput screening using a photo-induced electron transfer (PET) system to identify an inhibitor of NS3 helicase from marine organism extracts. We successfully identified psammaplin A as a novel NS3 inhibitor. The dose-response relationship clearly demonstrates the inhibition of NS3 RNA helicase and ATPase activities by psammaplin A, with IC₅₀ values of 17 and 32 μM, respectively. Psammaplin A has no influence on the apparent Km value (0.4 mM) of NS3 ATPase activity, and acts as a non-competitive inhibitor. Additionally, it inhibits the binding of NS3 to single-stranded RNA in a dose-dependent manner. Furthermore, psammaplin A shows an inhibitory effect on viral replication, with EC₅₀ values of 6.1 and 6.3 μM in subgenomic replicon cells derived from genotypes 1b and 2a, respectively. We postulate that psammaplin A is a potential anti-viral agent through the inhibition of ATPase, RNA binding and helicase activities of NS3. - Mast Cells Play a Key Role in Host Defense against Herpes Simplex Virus Infection through TNF-alpha and IL-6 Production
Rui Aoki; Tatsuyoshi Kawamura; Fumi Goshima; Youichi Ogawa; Susumu Nakae; Atsuhito Nakao; Kohji Moriishi; Yukihiro Nishiyama; Shinji Shimada
JOURNAL OF INVESTIGATIVE DERMATOLOGY, 133, 9, 2170, 2179, Sep. 2013, [Peer-reviewed]
English, Scientific journal - Serum RANTES level influences the response to pegylated interferon and ribavirin therapy in chronic hepatitis C
Kazuki Komase; Shinya Maekawa; Mika Miura; Ryota Sueki; Makoto Kadokura; Hiroko Shindo; Kuniaki Shindo; Fumitake Amemiya; Yasuhiro Nakayama; Taisuke Inoue; Minoru Sakamoto; Atsuya Yamashita; Kohji Moriishi; Nobuyuki Enomoto
HEPATOLOGY RESEARCH, 43, 8, 865, 875, Aug. 2013, [Peer-reviewed]
English, Scientific journal - Ca2+/S100 proteins regulate HCV virus NS5A-FKBP8/FKBP38 interaction and HCV virus RNA replication
Joji Tani; Seiko Shimamoto; Kyoko Mori; Nobuyuki Kato; Kohji Moriishi; Yoshiharu Matsuura; Hiroshi Tokumitsu; Mitsumasa Tsuchiya; Tomohito Fujimoto; Kiyohito Kato; Hisaaki Miyoshi; Tsutomu Masaki; Ryoji Kobayashi
LIVER INTERNATIONAL, 33, 7, 1008, 1018, Aug. 2013, [Peer-reviewed]
English, Scientific journal - Microglia release ATP by exocytosis
Yoshio Imura; Yosuke Morizawa; Ryohei Komatsu; Keisuke Shibata; Youichi Shinozaki; Hirotake Kasai; Kohji Moriishi; Yoshinori Moriyama; Schuichi Koizumi
GLIA, 61, 8, 1320, 1330, Aug. 2013, [Peer-reviewed]
English, Scientific journal - Understanding the Biological Context of NS5A-Host Interactions in HCV Infection: A Network-Based Approach
Lokesh P. Tripathi; Hiroto Kambara; Yi-An Chen; Yorihiro Nishimura; Kohji Moriishi; Toru Okamoto; Eiji Morita; Takayuki Abe; Yoshio Mori; Yoshiharu Matsuura; Kenji Mizuguchi
JOURNAL OF PROTEOME RESEARCH, 12, 6, 2537, 2551, Jun. 2013, [Peer-reviewed]
English, Scientific journal - Effects of immunization of pregnant guinea pigs with guinea pig cytomegalovirus glycoprotein B on viral spread in the placenta
Kaede Hashimoto; Souichi Yamada; Harutaka Katano; Saki Fukuchi; Yuko Sato; Minami Kato; Toyofumi Yamaguchi; Kohji Moriishi; Naoki Inoue
VACCINE, 31, 31, 3199, 3205, Jun. 2013, [Peer-reviewed]
English, Scientific journal - IL-28B (IFN-λ3) and IFN-α synergistically inhibit HCV replication
H. Shindo; S. Maekawa; K. Komase; M. Miura; M. Kadokura; R. Sueki; N. Komatsu; K. Shindo; F. Amemiya; Y. Nakayama; T. Inoue; M. Sakamoto; A. Yamashita; K. Moriishi; N. Enomoto
Journal of Viral Hepatitis, 20, 4, 281, 289, Apr. 2013, [Peer-reviewed]
English, Scientific journal - Antimicrobial Peptide LL-37 Produced by HSV-2-Infected Keratinocytes Enhances HIV Infection of Langerhans Cells
Youichi Ogawa; Tatsuyoshi Kawamura; Takamitsu Matsuzawa; Rui Aoki; Peter Gee; Atsuya Yamashita; Kohji Moriishi; Kenshi Yamasaki; Yoshio Koyanagi; Andrew Blauvelt; Shinji Shimada
CELL HOST & MICROBE, 13, 1, 77, 86, Jan. 2013, [Peer-reviewed]
English, Scientific journal - Inhibition of Both Protease and Helicase Activities of Hepatitis C Virus NS3 by an Ethyl Acetate Extract of Marine Sponge Amphimedon sp.
Yuusuke Fujimoto; Kazi Abdus Salam; Atsushi Furuta; Yasuyoshi Matsuda; Osamu Fujita; Hidenori Tani; Masanori Ikeda; Nobuyuki Kato; Naoya Sakamoto; Shinya Maekawa; Nobuyuki Enomoto; Nicole J. de Voogd; Masamichi Nakakoshi; Masayoshi Tsubuki; Yuji Sekiguchi; Satoshi Tsuneda; Nobuyoshi Akimitsu; Naohiro Noda; Atsuya Yamashita; Junichi Tanaka; Kohji Moriishi
PLOS ONE, 7, 11, e48685, Nov. 2012, [Peer-reviewed], [Last author, Corresponding author]
English, Scientific journal - Proteomic Analysis of Hepatitis C Virus (HCV) Core Protein Transfection and Host Regulator PA28 gamma Knockout in HCV Pathogenesis: A Network-Based Study
Lokesh P. Tripathi; Hiroto Kambara; Kohji Moriishi; Eiji Morita; Takayuki Abe; Yoshio Mori; Yi-An Chen; Yoshiharu Matsuura; Kenji Mizuguchi
JOURNAL OF PROTEOME RESEARCH, 11, 7, 3664, 3679, Jul. 2012, [Peer-reviewed]
English, Scientific journal - CD44 Participates in IP-10 Induction in Cells in Which Hepatitis C Virus RNA Is Replicating, through an Interaction with Toll-Like Receptor 2 and Hyaluronan
Takayuki Abe; Takasuke Fukuhara; Xiauyu Wen; Akinori Ninomiya; Kohji Moriishi; Yoshihiko Maehara; Osamu Takeuchi; Taro Kawai; Shizuo Akira; Yoshiharu Matsuura
JOURNAL OF VIROLOGY, 86, 11, 6159, 6170, Jun. 2012, [Peer-reviewed]
English, Scientific journal - Inhibition of Hepatitis C Virus NS3 Helicase by Manoalide
Kazi Abdus Salam; Atsushi Furuta; Naohiro Noda; Satoshi Tsuneda; Yuji Sekiguchi; Atsuya Yamashita; Kohji Moriishi; Masamichi Nakakoshi; Masayoshi Tsubuki; Hidenori Tani; Junichi Tanaka; Nobuyoshi Akimitsu
JOURNAL OF NATURAL PRODUCTS, 75, 4, 650, 654, Apr. 2012, [Peer-reviewed]
English, Scientific journal - Inhibition of Hepatitis C Virus Replication and Viral Helicase by Ethyl Acetate Extract of the Marine Feather Star Alloeocomatella polycladia
Atsuya Yamashita; Kazi Abdus Salam; Atsushi Furuta; Yasuyoshi Matsuda; Osamu Fujita; Hidenori Tani; Yoshihisa Fujita; Yuusuke Fujimoto; Masanori Ikeda; Nobuyuki Kato; Naoya Sakamoto; Shinya Maekawa; Nobuyuki Enomoto; Masamichi Nakakoshi; Masayoshi Tsubuki; Yuji Sekiguchi; Satoshi Tsuneda; Nobuyoshi Akimitsu; Naohiro Noda; Junichi Tanaka; Kohji Moriishi
MARINE DRUGS, 10, 4, 744, 761, Apr. 2012, [Peer-reviewed], [Last author, Corresponding author]
English, Scientific journal - Baculovirus GP64-Mediated Entry into Mammalian Cells
Chikako Kataoka; Yuuki Kaname; Shuhei Taguwa; Takayuki Abe; Takasuke Fukuhara; Hideki Tani; Kohji Moriishi; Yoshiharu Matsuura
JOURNAL OF VIROLOGY, 86, 5, 2610, 2620, Mar. 2012, [Peer-reviewed]
English, Scientific journal - Upregulation of nuclear PA28 gamma expression in cirrhosis and hepatocellular carcinoma
Motoi Kondo; Kohji Moriishi; Hiroshi Wada; Takehiro Noda; Shigeru Marubashi; Kenichi Wakasa; Yoshiharu Matsuura; Yuichiro Doki; Masaki Mori; Hiroaki Nagano
EXPERIMENTAL AND THERAPEUTIC MEDICINE, 3, 3, 379, 385, Mar. 2012, [Peer-reviewed]
English, Scientific journal - Exploitation of lipid components by viral and host proteins for hepatitis C virus infection
Kohji Moriishi; Yashiharu Matsuura
FRONTIERS IN MICROBIOLOGY, 3, 54, 2012, [Peer-reviewed], [Lead author, Corresponding author]
English - Dysfunction of Autophagy Participates in Vacuole Formation and Cell Death in Cells Replicating Hepatitis C Virus
Shuhei Taguwa; Hiroto Kambara; Naonobu Fujita; Takeshi Noda; Tamotsu Yoshimori; Kazuhiko Koike; Kohji Moriishi; Yoshiharu Matsuura
JOURNAL OF VIROLOGY, 85, 24, 13185, 13194, Dec. 2011, [Peer-reviewed]
English, Scientific journal - Heterogeneous Nuclear Ribonucleoprotein A2 Participates in the Replication of Japanese Encephalitis Virus through an Interaction with Viral Proteins and RNA
Hiroshi Katoh; Yoshio Mori; Hiroto Kambara; Takayuki Abe; Takasuke Fukuhara; Eiji Morita; Kohji Moriishi; Wataru Kamitani; Yoshiharu Matsuura
JOURNAL OF VIROLOGY, 85, 21, 10976, 10988, Nov. 2011, [Peer-reviewed]
English, Scientific journal - Activation of the Long Terminal Repeat of Human Endogenous Retrovirus K by Melanoma-Specific Transcription Factor MITF-M
Iyoko Katoh; Anna Mirova; Shun-ichi Kurata; Yasushi Murakami; Kenji Horikawa; Natsuko Nakakuki; Takunobu Sakai; Kunihiko Hashimoto; Ayako Maruyama; Takaaki Yonaga; Nahoko Fukunishi; Kohji Moriishi; Hirohisa Hirai
NEOPLASIA, 13, 11, 1081, U133, Nov. 2011, [Peer-reviewed]
English, Scientific journal - Will There Be an HCV Meeting in 2020? Summary of the 17th International Meeting on Hepatitis C Virus and Related Viruses
Takaji Wakita; Tetsuro Suzuki; Matthew J. Evans; Kunitada Shimotohno; Kazuaki Chayama; Yoshiharu Matsuura; Makoto Hijikata; Kohji Moriishi; Tsukasa Seya; Nobuyuki Enomoto; Kazuhiko Koike; Nobuyuki Kato; Tatsuya Kanto; Hak Hotta
GASTROENTEROLOGY, 141, 1, E1, E5, Jul. 2011, [Peer-reviewed]
English - [Functions of host factors regarding HCV pathogenicity].
Moriishi K
Nihon rinsho. Japanese journal of clinical medicine, 69 Suppl 4, 103, 108, May 2011, [Peer-reviewed] - Involvement of cyclophilin B in the replication of Japanese encephalitis virus
Hiroto Kambara; Hideki Tani; Yoshio Mori; Takayuki Abe; Hiroshi Katoh; Takasuke Fukuhara; Shuhei Taguwa; Kohji Moriishi; Yoshiharu Matsuura
VIROLOGY, 412, 1, 211, 219, Mar. 2011, [Peer-reviewed]
English, Scientific journal - Elimination of Hepatitis C Virus from Hepatocytes by a Selective Activation of Therapeutic Molecules
Xiaoyu Wen; Takayuki Abe; Hiroshi Kukihara; Shuhei Taguwa; Yoshio Mori; Hideki Tani; Nobuyuki Kato; Tetsuro Suzuki; Masashi Tatsumi; Kohji Moriishi; Yoshiharu Matsuura
PLOS ONE, 6, 1, e15967, Jan. 2011, [Peer-reviewed]
English, Scientific journal - Induction of ΔNp63 by the newly identified keratinocyte-specific transforming growth factor βsignaling pathway with smad2 and IkB kinase α in squamous cell carcinoma1,2
Nahoko FUKUNISHI; Iyoko KATOH; Yoshiya TOMIMORI; Keiichi TSUKINOKI; Ryu-Ichiro HATA; Atsuhito NAKAO; Yoji IKAWA; Shun-ichi KURATA
NEOPLASIA, 12, 12, 969, 979, Elsevier B.V., 01 Dec. 2010, [Peer-reviewed]
English, Scientific journal - Involvement of PA28 gamma in the Propagation of Hepatitis C Virus
Kohji Moriishi; Ikuo Shoji; Yoshio Mori; Ryosuke Suzuki; Tetsuro Suzuki; Chikako Kataoka; Yoshiharu Matsuura
HEPATOLOGY, 52, 2, 411, 420, Aug. 2010, [Peer-reviewed], [Lead author]
English, Scientific journal - Acquisition of Complement Resistance through Incorporation of CD55/Decay-Accelerating Factor into Viral Particles Bearing Baculovirus GP64
Yuuki Kaname; Hideki Tani; Chikako Kataoka; Mai Shiokawa; Shuhei Taguwa; Takayuki Abe; Kohji Moriishi; Taroh Kinoshita; Yoshiharu Matsuura
JOURNAL OF VIROLOGY, 84, 7, 3210, 3219, Apr. 2010, [Peer-reviewed]
English, Scientific journal - Establishment of an indicator cell system for hepatitis C virus
Yoshinori Tanaka; Yoshio Mori; Hideki Tani; Takayuki Abe; Kohji Moriishi; Hirotatsu Kojima; Tetsuo Nagano; Takayoshi Okabe; Tetsuro Suzuki; Masashi Tatsumi; Yoshiharu Matsuura
MICROBIOLOGY AND IMMUNOLOGY, 54, 4, 206, 220, Apr. 2010, [Peer-reviewed]
English, Scientific journal - Involvement of Ceramide in the Propagation of Japanese Encephalitis Virus
Hideki Tani; Mai Shiokawa; Yuuki Kaname; Hiroto Kambara; Yoshio Mori; Takayuki Abe; Kohji Moriishi; Yoshiharu Matsuura
JOURNAL OF VIROLOGY, 84, 6, 2798, 2807, Mar. 2010, [Peer-reviewed]
English, Scientific journal - Peripheral B Cells May Serve as a Reservoir for Persistent Hepatitis C Virus Infection
Masahiko Ito; Atsuko Masumi; Keiko Mochida; Hiroshi Kukihara; Kohji Moriishi; Yoshiharu Matsuura; Kazunari Yamaguchi; Toshiaki Mizuochi
JOURNAL OF INNATE IMMUNITY, 2, 6, 607, 617, 2010, [Peer-reviewed]
English, Scientific journal - Network based analysis of hepatitis C virus Core and NS4B protein interactions
Lokesh P. Tripathi; Chikako Kataoka; Shuhei Taguwa; Kohji Moriishi; Yoshio Mori; Yoshiharu Matsuura; Kenji Mizuguchi
MOLECULAR BIOSYSTEMS, 6, 12, 2539, 2553, 2010, [Peer-reviewed]
English, Scientific journal - Cochaperone Activity of Human Butyrate-Induced Transcript 1 Facilitates Hepatitis C Virus Replication through an Hsp90-Dependent Pathway
Shuhei Taguwa; Hiroto Kambara; Hiroko Omori; Hideki Tani; Takayuki Abe; Yoshio Mori; Tetsuro Suzuki; Tamotsu Yoshimori; Kohji Moriishi; Yoshiharu Matsuura
JOURNAL OF VIROLOGY, 83, 20, 10427, 10436, Oct. 2009, [Peer-reviewed]
English, Scientific journal - Tacrolimus Ameliorates Metabolic Disturbance and Oxidative Stress Caused by Hepatitis C Virus Core Protein Analysis Using Mouse Model and Cultured Cells
Kyoji Moriya; Hideyuki Miyoshi; Takeya Tsutsumi; Seiko Shinzawa; Hajime Fujie; Yoshizumi Shintani; Hiroshi Yotsuyanagi; Kohji Moriishi; Yoshiharu Matsuura; Tetsuro Suzuki; Tatsuo Miyamura; Kazuhiko Koike
AMERICAN JOURNAL OF PATHOLOGY, 175, 4, 1515, 1524, Oct. 2009, [Peer-reviewed]
English, Scientific journal - Baculovirus Induces Type I Interferon Production through Toll-Like Receptor-Dependent and -Independent Pathways in a Cell-Type-Specific Manner
Takayuki Abe; Yuuki Kaname; Xiaoyu Wen; Hideki Tani; Kohji Moriishi; Satoshi Uematsu; Osamu Takeuchi; Ken J. Ishii; Taro Kawai; Shizuo Akira; Yoshiharu Matsuura
JOURNAL OF VIROLOGY, 83, 15, 7629, 7640, Aug. 2009, [Peer-reviewed]
English, Scientific journal - Human VAP-C Negatively Regulates Hepatitis C Virus Propagation
Hiroshi Kukihara; Kohji Moriishi; Shuhei Taguwa; Hideki Tani; Takayuki Abe; Yoshio Mori; Tetsuro Suzuki; Takasuke Fukuhara; Akinobu Taketomi; Yoshihiko Maehara; Yoshiharu Matsuura
JOURNAL OF VIROLOGY, 83, 16, 7959, 7969, Aug. 2009, [Peer-reviewed]
English, Scientific journal - Biological and immunological characteristics of hepatitis E virus-like particles based on the crystal structure
Tetsuo Yamashita; Yoshio Mori; Naoyuki Miyazaki; R. Holland Cheng; Masato Yoshimura; Hideaki Unno; Ryoichi Shima; Kohji Moriishi; Tomitake Tsukihara; Tian Cheng Li; Naokazu Takeda; Tatsuo Miyamura; Yoshiharu Matsuura
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 106, 31, 12986, 12991, Aug. 2009, [Peer-reviewed]
English, Scientific journal - Proteasomal Turnover of Hepatitis C Virus Core Protein Is Regulated by Two Distinct Mechanisms: a Ubiquitin-Dependent Mechanism and a Ubiquitin-Independent but PA28 gamma-Dependent Mechanism
Ryosuke Suzuki; Kohji Moriishi; Kouichirou Fukuda; Masayuki Shirakura; Koji Ishii; Ikuo Shoji; Takaji Wakita; Tatsuo Miyamura; Yoshiharu Matsuura; Tetsuro Suzuki
JOURNAL OF VIROLOGY, 83, 5, 2389, 2392, Mar. 2009, [Peer-reviewed]
English, Scientific journal - [Processing and pathogenicity of HCV core protein].
Moriishi K; Mori Y; Matsuura Y
Uirusu, 58, 2, 183, 190, Dec. 2008, [Peer-reviewed] - Intramembrane processing by signal peptide peptidase regulates the membrane localization of hepatitis C virus core protein and viral propagation
Kiyoko Okamoto; Yoshio Mori; Yasumasa Komoda; Toru Okamoto; Masayasu Okochi; Masatoshi Takeda; Tetsuro Suzuki; Kohji Moriishi; Yoshiharu Matsuura
JOURNAL OF VIROLOGY, 82, 17, 8349, 8361, Sep. 2008, [Peer-reviewed]
English, Scientific journal - Crystal structure of the catalytic domain of Japanese encephalitis virus NS3 helicase/nucleoside triphosphatase at a resolution of 1.8 angstrom
Tetsuo Yamashita; Hideaki Unno; Yoshio Mori; Hideki Tani; Kohji Moriishi; Akihisa Takamizawa; Masanobu Agoh; Tomitake Tsukihara; Yoshiharu Matsuura
VIROLOGY, 373, 2, 426, 436, Apr. 2008, [Peer-reviewed]
English, Scientific journal - A single-amino-acid mutation in hepatitis C virus NS5A disrupting FKBP8 interaction impairs viral replication
Toru Okamoto; Hiroko Omori; Yuuki Kaname; Takayuki Abe; Yorihiro Nishimura; Tetsuro Suzuki; Tatsuo Miyamura; Tamotsu Yoshimori; Kohji Moriishi; Yoshiharu Matsuura
JOURNAL OF VIROLOGY, 82, 7, 3480, 3489, Apr. 2008, [Peer-reviewed]
English, Scientific journal - Human butyrate-induced transcript 1 interacts with hepatitis C virus NS5A and regulates viral replication
Shuhei Taguwa; Toru Okamoto; Takayuki Abe; Yoshio Mori; Tetsuro Suzuki; Kohji Moriishi; Yoshiharu Matsuura
JOURNAL OF VIROLOGY, 82, 6, 2631, 2641, Mar. 2008, [Peer-reviewed]
English, Scientific journal - Virus-cell interaction of HCV
Hideki Tani; Yasumasa Komoda; Chang-Kwang Limn; Kensuke Suzuki; Kohji Moriishi; Tatsuo Miyamura; Yoshiharu Matsuura
Structure-Based Study of Viral Replication: (With CD-Rom), 125, 150, World Scientific Publishing Co., 01 Jan. 2008, [Peer-reviewed]
English, In book - Hepatitis C virus core protein: Its coordinate roles with PA28 gamma in metabolic abnormality and carcinogenicity in the liver
Yoshio Mori; Kohji Moriishi; Yoshiharu Matsuura
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY, 40, 8, 1437, 1442, 2008, [Peer-reviewed]
English, Scientific journal - [Pathogenesis of hepatitis C virus].
Moriishi K; Matsuura Y
Uirusu, 57, 2, 141, 149, Dec. 2007, [Peer-reviewed] - Evaluation systems for anti-HCV drugs
Kohji Moriishi; Yoshiharu Matsuura
ADVANCED DRUG DELIVERY REVIEWS, 59, 12, 1213, 1221, Oct. 2007, [Peer-reviewed]
English - Host factors involved in the replication of hepatitis C virus
Kohji Moriishi; Yoshiharu Matsuura
REVIEWS IN MEDICAL VIROLOGY, 17, 5, 343, 354, Sep. 2007, [Peer-reviewed]
English - Hepatitis C virus nonstructural protein 5A modulates the toll-like receptor-MyD88-dependent signaling pathway in macrophage cell lines
Takayuki Abe; Yuuki Kaname; Itsuki Hamamoto; Yoshimi Tsuda; Xiaoyu Wen; Shuhei Taguwa; Kohji Moriishi; Osamu Takeuchi; Taro Kawai; Tatsuya Kanto; Norio Hayashi; Shizuo Akira; Yoshiharu Matsuura
JOURNAL OF VIROLOGY, 81, 17, 8953, 8966, Sep. 2007, [Peer-reviewed]
English, Scientific journal - Processsing of capsid protein by Cathepsin L plays a crucial role in replication of Japanese encephalitis virus in neural and macrophage cells
Yoshio Mori; Tetsuo Yamashita; Yoshinori Tanaka; Yoshimi Tsuda; Takayuki Abe; Kohji Moriishi; Yoshiharu Matsuura
JOURNAL OF VIROLOGY, 81, 16, 8477, 8487, Aug. 2007, [Peer-reviewed]
English, Scientific journal - Replication-competent recombinant vesicular stomatitis virus encoding hepatitis C virus envelope proteins
Hideki Tani; Yasumasa Komoda; Eiko Matsuo; Kensuke Suzuki; Itsuki Hamamoto; Tetsuo Yamashita; Kohji Moriishi; Kazuhito Fujiyama; Tatsuya Kanto; Norio Harashi; Ania Owsianka; Arvind H. Patel; Michael A. Whitt; Yoshiharu Matsuura
JOURNAL OF VIROLOGY, 81, 16, 8601, 8612, Aug. 2007, [Peer-reviewed]
English, Scientific journal - E6AP ubiquitin ligase mediates ubiquitylation and degradation of hepatitis C virus core protein
Masayuki Shirakura; Kyoko Murakami; Tohru Ichimura; Ryosuke Suzuki; Tetsu Shimoji; Kouichirou Fukuda; Katsutoshi Abe; Shigeko Sato; Masayoshi Fukasawa; Yoshio Yamakawa; Masahiro Nishijima; Kohji Moriishi; Yoshiharu Matsuura; Takaji Wakita; Tetsuro Suzuki; Peter M. Howley; Tatsuo Miyamura; Ikuo Shoji
JOURNAL OF VIROLOGY, 81, 3, 1174, 1185, Feb. 2007, [Peer-reviewed]
English, Scientific journal - Involvement of the PA28 gamma-dependent pathway in insulin resistance induced by hepatitis C virus core protein
Hironobu Miyamoto; Kohji Moriishi; Kyoji Moriya; Shigeo Murata; Keiji Tanaka; Tetsuro Suzuki; Tatsuo Miyamura; Kazuhiko Koike; Yoshiharu Matsuura
JOURNAL OF VIROLOGY, 81, 4, 1727, 1735, Feb. 2007, [Peer-reviewed], [Lead author, Corresponding author]
English, Scientific journal - Critical role of PA28 gamma in hepatitis C virus-associated steatogenesis and hepatocarcinogenesis
Kohji Moriishi; Rika Mochizuki; Kyoji Moriya; Hironobu Miyamoto; Yoshio Mori; Takayuki Abe; Shigeo Murata; Keiji Tanaka; Tatsuo Miyamura; Tetsuro Suzuki; Kazuhiko Koiket; Yoshiharu Matsuura
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 104, 5, 1661, 1666, Jan. 2007, [Peer-reviewed]
English, Scientific journal - Oligomerization of hepatitis C virus core protein is crucial for interaction with the cytoplasmic domain of E1 envelope protein
Kousuke Nakai; Toru Okamoto; Tomomi Kimura-Someya; Koji Ishii; Chang Kweng Lim; Hideki Tani; Eiko Matsuo; Takayuki Abe; Yoshio Mori; Tetsuro Suzuki; Tatsuo Miyamura; Jack H. Nunberg; Kohji Moriishi; Yoshiharu Matsuura
JOURNAL OF VIROLOGY, 80, 22, 11265, 11273, Nov. 2006, [Peer-reviewed]
English, Scientific journal - Hepatitis C virus RNA replication is regulated by FKBP8 and Hsp90
Toru Okamoto; Yorihiro Nishimura; Tohru Ichimura; Kensuke Suzuki; Tatsuo Miyamura; Tetsuro Suzuki; Kohji Moriishi; Yoshiharu Matsuura
EMBO JOURNAL, 25, 20, 5015, 5025, Oct. 2006, [Peer-reviewed]
English, Scientific journal - Characterization of HCV-like particles produced in a human hepatoma cell line by a recombinant baculovirus
E Matsuo; H Tani; CK Lim; Y Komoda; T Okamoto; H Miyamoto; K Moriishi; S Yagi; AH Patel; T Miyamura; Y Matsuura
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 340, 1, 200, 208, Feb. 2006, [Peer-reviewed]
English, Scientific journal - Nucleolar protein B23 interacts with Japanese encephalitis virus core protein and participates in viral replication
Y Tsuda; Y Mori; T Abe; T Yamashita; T Okamoto; T Ichimura; K Moriishi; Y Matsuura
MICROBIOLOGY AND IMMUNOLOGY, 50, 3, 225, 234, 2006, [Peer-reviewed]
English, Scientific journal - Human VAP-B is involved in hepatitis C virus replication through interaction with NS5A and NS5B
Hamamoto, I; Y Nishimura; T Okamoto; H Aizaki; MY Liu; Y Mori; T Abe; T Suzuki; MMC Lai; T Miyamura; K Moriishi; Y Matsuura
JOURNAL OF VIROLOGY, 79, 21, 13473, 13482, Nov. 2005, [Peer-reviewed]
English, Scientific journal - Involvement of the toll-like receptor 9 signaling pathway in the induction of innate immunity by baculovirus
T Abe; H Hemmi; H Miyamoto; K Moriishi; S Tamura; H Takaku; S Akira; Y Matsuura
JOURNAL OF VIROLOGY, 79, 5, 2847, 2858, Mar. 2005, [Peer-reviewed]
English, Scientific journal - Nuclear localization of Japanese encephalitis virus core protein enhances viral replication
Y Mori; T Okabayashi; T Yamashita; ZJ Zhao; T Wakita; K Yasui; F Hasebe; M Tadano; E Konishi; K Moriishi; Y Matsuura
JOURNAL OF VIROLOGY, 79, 6, 3448, 3458, Mar. 2005, [Peer-reviewed]
English, Scientific journal - Ligand-directed gene targeting to mammalian cells by pseudotype baculoviruses
Y Kitagawa; H Tani; C Kwang; LTM Matsunaga; K Moriishi; Y Matsuura
JOURNAL OF VIROLOGY, 79, 6, 3639, 3652, Mar. 2005, [Peer-reviewed]
English, Scientific journal - Molecular determinants for subcellular localization of hepatitis C virus core protein
R Suzuki; S Sakamoto; T Tsutsumi; A Rikimaru; K Tanaka; T Shimoike; K Moriishi; T Iwasaki; K Mizumoto; Y Matsuura; T Miyamura; T Suzuki
JOURNAL OF VIROLOGY, 79, 2, 1271, 1281, Jan. 2005, [Peer-reviewed]
English, Scientific journal - [Development of HCV vaccine].
Abe T; Moriishi K; Matsuura Y
Nihon rinsho. Japanese journal of clinical medicine, 62 Suppl 7, Pt 1, 139, 142, Jul. 2004, [Peer-reviewed] - [Candidate molecules for HCV receptor].
Moriishi K; Limn CK; Matsuura Y
Nihon rinsho. Japanese journal of clinical medicine, 62 Suppl 7, Pt 1, 191, 194, Jul. 2004, [Peer-reviewed] - Intramembrane proteolysis and endoplasmic reticulum retention of hepatitis C virus core protein
K Okamoto; K Moriishi; T Miyamura; Y Matsuura
JOURNAL OF VIROLOGY, 78, 12, 6370, 6380, Jun. 2004, [Peer-reviewed]
English, Scientific journal - [Baculovirus vector--gene transfer into mammalian cells].
Tani H; Abe T; Limn CK; Mochizuki R; Yamagishi J; Kitagawa Y; Watanabe R; Moriishi K; Matsuura Y
Uirusu, 53, 2, 185, 193, Dec. 2003, [Peer-reviewed] - Proteasome activator PA28 gamma-dependent nuclear retention and degradation of hepatitis C virus core protein
K Moriishi; T Okabayashi; K Nakai; K Moriya; K Koike; S Murata; T Chiba; K Tanaka; R Suzuki; T Suzuki; T Miyamura; Y Matsuura
JOURNAL OF VIROLOGY, 77, 19, 10237, 10249, Oct. 2003, [Peer-reviewed], [Lead author]
English, Scientific journal - In vitro and in vivo gene delivery by recombinant baculoviruses
H Tani; CK Limn; CC Yap; M Onishi; M Nozaki; Y Nishimune; N Okahashi; Y Kitagawa; R Watanabe; R Mochizuki; K Moriishi; Y Matsuura
JOURNAL OF VIROLOGY, 77, 18, 9799, 9808, Sep. 2003, [Peer-reviewed]
English, Scientific journal - Mechanisms of hepatitis C virus infection
Kohji Moriishi; Yoshiharu Matsuura
Antiviral Chemistry and Chemotherapy, 14, 6, 285, 297, International Medical Press Ltd, 2003, [Peer-reviewed]
English - Induction of Bad-mediated apoptosis by Sindbis virus infection: Involvement of pro-survival members of the Bcl-2 family
K Moriishi; M Koura; Y Matsuura
VIROLOGY, 292, 2, 258, 271, Jan. 2002, [Peer-reviewed]
English, Scientific journal - Characterization of pseudotype VSV possessing HCV envelope proteins
Y Matsuura; H Tani; K Suzuki; T Kimura-Someya; R Suzuki; H Aizaki; K Ishii; K Moriishi; CS Robison; MA Whitt; T Miyamura
VIROLOGY, 286, 2, 263, 275, Aug. 2001, [Peer-reviewed]
English, Scientific journal - Tissue expression and subcellular localization of the pro-survival molecule Bcl-w
LA O'Reilly; C Print; G Hausmann; K Morlishi; S Cory; DCS Huang; A Strasser
CELL DEATH AND DIFFERENTIATION, 8, 5, 486, 494, May 2001, [Peer-reviewed]
English, Scientific journal - Inhibition of listeriolysin O-induced hemolysis by bovine lactoferrin
K Moriishi; S Inoue; M Koura; F Amano
BIOLOGICAL & PHARMACEUTICAL BULLETIN, 22, 11, 1167, 1172, Nov. 1999, [Peer-reviewed]
English, Scientific journal - Neuronal and glial differentiation of neuroblastoma and glioma cells by Rho inhibitory bacterial exo-enzyme C3
R Komagome; B Shuto; K Moriishi; K Kimura; M Saito
NEUROPATHOLOGY, 19, 3, 288, 293, Sep. 1999, [Peer-reviewed]
English, Scientific journal - Bcl-2 family members do not inhibit apoptosis by binding the caspase activator Apaf-1
K Moriishi; DCS Huang; S Cory; JM Adams
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 96, 17, 9683, 9688, Aug. 1999, [Peer-reviewed]
English, Scientific journal - Control of apoptosis in hematopoietic cells by the Bcl-2 family of proteins
JM Adams; DCS Huang; H Puthalakath; P Bouillet; G Vairo; K Moriishi; G Hausmann; L O'Reilly; K Newton; S Ogilvy; ML Bath; CG Print; AW Harris; A Strasser; S Cory
COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY, 64, 351, 358, 1999, [Peer-reviewed]
English, Scientific journal - Tyrosine phosphorylation as a convergent pathway of heterotrimeric G protein- and rho protein-mediated Ca2+ sensitization of smooth muscle of rabbit mesenteric artery
M Sasaki; Y Hattori; F Tomita; K Moriishi; M Kanno; T Kohya; K Oguma; A Kitabatake
BRITISH JOURNAL OF PHARMACOLOGY, 125, 8, 1651, 1660, Dec. 1998, [Peer-reviewed]
English, Scientific journal - Rapid hybridoma screening method for the identification of monoclonal antibodies to low-abundance cytoplasmic proteins
LA O'Reilly; L Cullen; K Moriishi; L O'Connor; DCS Huang; A Strasser
BIOTECHNIQUES, 25, 5, 824, +, Nov. 1998, [Peer-reviewed]
English, Scientific journal - Sequence analysis of the actA gene of Listeria monocytogenes isolated from human
K Moriishi; M Terao; M Koura; S Inoue
MICROBIOLOGY AND IMMUNOLOGY, 42, 2, 129, 132, 1998, [Peer-reviewed]
English, Scientific journal - Epitope regions in the heavy chain of Clostridium botulinum type E neurotoxin recognized by monoclonal antibodies
T Kubota; T Watanabe; N Yokosawa; K Tsuzuki; T Indoh; K Moriishi; K Sanda; Y Maki; K Inoue; N Fujii
APPLIED AND ENVIRONMENTAL MICROBIOLOGY, 63, 4, 1214, 1218, Apr. 1997, [Peer-reviewed]
English, Scientific journal - Expression of listeriolysin O by intracellular Listeria monocytogenes following infection of lipopolysaccharide-treated or untreated J774.1 macrophage-like cells
K Moriishi; M Koura; F Amano
FEMS IMMUNOLOGY AND MEDICAL MICROBIOLOGY, 16, 3-4, 213, 222, Dec. 1996, [Peer-reviewed]
English, Scientific journal - Expression of listeriolysin O by intracellular Listeria monocytogenes following infection of lipopolysaccharide-treated or untreated J774.1 macrophage-like cells
K Moriishi; M Koura; F Amano
FEMS IMMUNOLOGY AND MEDICAL MICROBIOLOGY, 16, 3-4, 213, 222, Dec. 1996, [Peer-reviewed]
English, Scientific journal - Studying on botulinum C2 toxin gene
T Kubota; K Kimura; Ohishi, I; K Moriishi; E Isogai; H Isogai; N Fujii
JAPANESE JOURNAL OF MEDICAL SCIENCE & BIOLOGY, 49, 5-6, 267, 269, Oct. 1996, [Peer-reviewed]
English, Scientific journal - Mosaic structures of neurotoxins produced from Clostridium botulinum types C and D organisms
K Moriishi; M Koura; N Abe; N Fujii; Y Fujinaga; K Inoue; K Ogumad
BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION, 1307, 2, 123, 126, Jun. 1996, [Peer-reviewed]
English, Scientific journal - Mosaic structures of neurotoxins produced from Clostridium botulinum types C and D organisms.
Moriishi K; Koura M; Abe N; Fujii N; Fujinaga Y; Inoue K; Ogumad K
Biochimica et biophysica acta, 1307, 2, 123, 126, Jun. 1996, [Peer-reviewed] - Molecular composition of Clostridium botulinum type A progenitor toxins
K Inoue; Y Fujinaga; T Watanabe; T Ohyama; K Takeshi; K Moriishi; H Nakajima; K Inoue; K Oguma
INFECTION AND IMMUNITY, 64, 5, 1589, 1594, May 1996, [Peer-reviewed]
English, Scientific journal - Characterization of component-I gene of botulinum C2 toxin and PCR detection of its gene in clostridial species
N Fujii; T Kubota; S Shirakawa; K Kimura; Ohishi, I; K Moriishi; E Isogai; H Isogai
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 220, 2, 353, 359, Mar. 1996, [Peer-reviewed]
English, Scientific journal - Molecular cloning of the gene encoding the mosaic neurotoxin: Composed of parts of botulinum neurotoxin types C1 and D, and PCR detection of this gene from Clostridium botulinum type C organisms
K Moriishi; M Koura; N Fujii; Y Fujinaga; K Inoue; B Syuto; K Oguma
APPLIED AND ENVIRONMENTAL MICROBIOLOGY, 62, 2, 662, 667, Feb. 1996, [Peer-reviewed]
English, Scientific journal - Molecular composition of progenitor toxins produced by C-botulinum types A and D
K Inoue; Y Fujinaga; T Watanabe; T Ohyama; K Moriishi; H Sunagawa; K Inoue; K Oguma
JAPANESE JOURNAL OF MEDICAL SCIENCE & BIOLOGY, 48, 5-6, 263, 264, Oct. 1995, [Peer-reviewed]
English, Scientific journal - TYPE-A AND B NEUROTOXIN GENES IN A CLOSTRIDIUM-BOTULINUM TYPE AB STRAIN
Y FUJINAGA; K TAKESHI; K INOUE; R FUJITA; T OHYAMA; K MORIISHI; K OGUMA
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 213, 3, 737, 745, Aug. 1995, [Peer-reviewed]
English, Scientific journal - INVOLVEMENT OF RHO IN GTP-GAMMA-S-INDUCED ENHANCEMENT OF PHOSPHORYLATION OF 20 KDA MYOSIN LIGHT-CHAIN IN VASCULAR SMOOTH-MUSCLE CELLS - INHIBITION OF PHOSPHATASE-ACTIVITY
M NODA; C YASUDAFUKAZAWA; K MORIISHI; T KATO; T OKUDA; K KUROKAWA; Y TAKUWA
FEBS LETTERS, 367, 3, 246, 250, Jul. 1995, [Peer-reviewed]
English, Scientific journal - INVOLVEMENT OF RHO IN GTP-GAMMA-S-INDUCED ENHANCEMENT OF PHOSPHORYLATION OF 20 KDA MYOSIN LIGHT-CHAIN IN VASCULAR SMOOTH-MUSCLE CELLS - INHIBITION OF PHOSPHATASE-ACTIVITY
M NODA; C YASUDAFUKAZAWA; K MORIISHI; T KATO; T OKUDA; K KUROKAWA; Y TAKUWA
FEBS LETTERS, 367, 3, 246, 250, Jul. 1995, [Peer-reviewed]
English, Scientific journal - IDENTIFICATION OF GANGLIOSIDES AS INHIBITORS OF ADP-RIBOSYLTRANSFERASES OF PERTUSSIS TOXIN AND EXOENZYME C3 FROM CLOSTRIDIUM-BOTULINUM
M HARAYOKOYAMA; Y HIRABAYASHI; F IRIE; B SYUTO; K MORIISHI; H SUGIYA; S FURUYAMA
JOURNAL OF BIOLOGICAL CHEMISTRY, 270, 14, 8115, 8121, Apr. 1995, [Peer-reviewed]
English, Scientific journal - 2 DIFFERENT TYPES OF ADP-RIBOSYLTRANSFERASE C3 FROM CLOSTRIDIUM-BOTULINUM TYPE D LYSOGENIZED ORGANISMS
K MORIISHI; B SYUTO; M SAITO; K OGUMA; N FUJII; N ABE; M NAIKI
INFECTION AND IMMUNITY, 61, 12, 5309, 5314, Dec. 1993, [Peer-reviewed]
English, Scientific journal - CONFIRMED NUCLEOTIDE-SEQUENCE OF FANF OF ESCHERICHIA-COLI K99 FIMBRIAE
N ABE; K MORIISHI; M SAITO; M NAIKI
JAPANESE JOURNAL OF VETERINARY RESEARCH, 41, 2-4, 97, 99, Nov. 1993, [Peer-reviewed]
English, Scientific journal - INHIBITION OF NOREPINEPHRINE SECRETION FROM DIGITONIN PERMEABILIZED PC12 CELLS BY BOTULINUM TYPE-D TOXIN
N YOKOSAWA; N FUJII; K TSUZUKI; K KIMURA; B SYUTO; K MORIISHI; K OGUMA
TOXICON, 30, 12, 1555, 1562, Dec. 1992, [Peer-reviewed]
English, Scientific journal - THE STRUCTURE GENES-CODING FOR THE NONTOXIC COMPONENT OF CLOSTRIDIUM-BOTULINUM TYPE-C AND TYPE-E PROGENITOR TOXINS
K TSUZUKI; N FUJII; K KIMURA; N YOKOSAWA; K MORIISHI; B SYUTO; K OGUMA
JAPANESE JOURNAL OF MEDICAL SCIENCE & BIOLOGY, 45, 5-6, 292, 294, Oct. 1992, [Peer-reviewed]
English, Scientific journal - EPIDERMAL-CELL DIFFERENTIATION INHIBITOR ADP-RIBOSYLATES SMALL GTP-BINDING PROTEINS AND INDUCES HYPERPLASIA OF EPIDERMIS
M SUGAI; K HASHIMOTO; A KIKUCHI; S INOUE; H OKUMURA; K MATSUMOTO; Y GOTO; H OHGAI; K MORIISHI; B SYUTO; K YOSHIKAWA; H SUGINAKA; Y TAKAI
JOURNAL OF BIOLOGICAL CHEMISTRY, 267, 4, 2600, 2604, Feb. 1992, [Peer-reviewed]
English, Scientific journal - CLONING AND WHOLE NUCLEOTIDE-SEQUENCE OF THE GENE FOR THE LIGHT CHAIN COMPONENT OF BOTULINUM TYPE-E TOXIN FROM CLOSTRIDIUM-BUTYRICUM STRAIN-BL6340 AND CLOSTRIDIUM-BOTULINUM TYPE-E STRAIN MASHIKE
N FUJII; K KIMURA; T YASHIKI; K TSUZUKI; K MORIISHI; N YOKOSAWA; B SYUTO; K OGUMA
MICROBIOLOGY AND IMMUNOLOGY, 36, 3, 213, 220, 1992, [Peer-reviewed]
English, Scientific journal - PURIFICATION AND CHARACTERIZATION OF ADP-RIBOSYLTRANSFERASES (EXOENZYME-C3) OF CLOSTRIDIUM-BOTULINUM TYPE-C AND TYPE-D STRAINS
K MORIISHI; B SYUTO; N YOKOSAWA; K OGUMA; M SAITO
JOURNAL OF BACTERIOLOGY, 173, 19, 6025, 6029, Oct. 1991, [Peer-reviewed]
English, Scientific journal - LOW-MOLECULAR-WEIGHT GTP-BINDING PROTEINS SERVING AS ADP-RIBOSYLATION SUBSTRATE FOR ADP-RIBOSYLTRANSFERASE FROM CLOSTRIDIUM-BOTULINUM AND THEIR RELATION TO PHOSPHOINOSITIDES METABOLISM IN THYMOCYTES
P WANG; J NISHIHATA; F MAKISHIMA; K MORIISHI; B SYUTO; S TOYOSHIMA; T OSAWA
JOURNAL OF BIOCHEMISTRY, 108, 5, 879, 885, Nov. 1990, [Peer-reviewed]
English, Scientific journal - SEPARATION OF TOXIC ACTIVITY AND ADP-RIBOSYLATION ACTIVITY OF BOTULINUM NEUROTOXIN-D
K MORIISHI; B SYUTO; K OGUMA; M SAITO
JOURNAL OF BIOLOGICAL CHEMISTRY, 265, 27, 16614, 16616, Sep. 1990, [Peer-reviewed]
English, Scientific journal - MOLECULAR DIVERSITY OF NEUROTOXINS FROM CLOSTRIDIUM-BOTULINUM TYPE-D STRAINS
K MORIISHI; B SYUTO; S KUBO; K OGUMA
INFECTION AND IMMUNITY, 57, 9, 2886, 2891, Sep. 1989, [Peer-reviewed]
English, Scientific journal - Botulinum neurotoxin D: Variations in molecular properties
K. Moriishi; B. Syuto; S. Kubo; K. Oguma
Japanese Journal of Medical Science and Biology, 42, 5-6, 181, 182, 1989
English, International conference proceedings - ADP-RIBOSYLATION OF 24-26-KDA GTP-BINDING PROTEINS LOCALIZED IN NEURONAL AND NON-NEURONAL CELLS BY BOTULINUM NEUROTOXIN-D
MATSUOKA, I; H SAKUMA; B SYUTO; K MORIISHI; S KUBO; K KURIHARA
JOURNAL OF BIOLOGICAL CHEMISTRY, 264, 2, 706, 712, Jan. 1989, [Peer-reviewed]
English, Scientific journal
- Antibodies targeting hepatitis B virus preS2 region inhibit the HBV infection
矢藤慶悟; 矢藤慶悟; 深野顕人; 松田麻未; 田中智久; 森石恆司; 西辻裕紀; 下遠野邦忠; 田村浩二; 加藤孝宣; 村松正道; 鈴木亮介; 鈴木亮介, 日本ウイルス学会学術集会プログラム・予稿集(Web), 68th, 2021 - Regulated disturbances of nucleocytoplasmic trafficking by SARS-CoV-2 ORF6
宮本洋一; 伊東祐美; 鈴木達也; 田中智久; 坂井祐介; 小井土大; 波田千彰; WANG Cai-Xia; 大谷真弓; 森石恆司; 立花太郎; 立花太郎; 鎌谷洋一郎; 米田悦啓; 岡本徹; 岡正啓, 日本細胞生物学会大会(Web), 73rd, 2021 - Generation of monoclonal antibodies against hepatitis B virus preS1 region from antigen‐specific memory B cells
YATO Keigo; YATO Keigo; ONODERA Taishi; MATSUDA Mami; FUJIMOTO Akira; WATASHI Koichi; AIZAKI Hideki; KATO Takanobu; MORIISHI Kohji; TAMURA Koji; TAKAHASHI Yoshimasa; WAKITA Takaji; MURAMATSU Masamichi; SUZUKI Ryosuke, 日本ウイルス学会学術集会プログラム・抄録集, 66th, 177, 18 Sep. 2018
English - 基礎研究医養成の試み 文部科学省GPプログラムの検証 リエゾンアカデミー研究医養成プログラム
小泉 修一; 中尾 篤人; 竹田 扇; 杉田 完爾; 大塚 稔久; 宮澤 恵二; 範 江林; 森石 恆司; 久保田 たけお; 武田 正之, 医学教育, 46, Suppl., 34, 34, Jul. 2015
(一社)日本医学教育学会, Japanese - Development of a cell culture and infection system for hepatitis B virus using 3D cultured non-neoplastic HuS-E/2 cells.
AKAHORI Yuichi; KATO Hiroki; FUJITA Takashi; MORIISHI Kohji; WATASHI Koichi; WAKITA Takajoi; HIJIKATA Makoto, 第63回日本ウイルス学会学術集会．福岡 2015年11月22-24日, 2015 - Development of a cell culture and infection system for hepatitis B virus using 3D cultured immortalized human hepatocytes.
AKAHORI Yuichi; KATO Hiroki; FUJITA Takashi; MORIISHI Kohji; WATASHI Koichi; WAKITA Takaji; HIJIKATA Makoto, 2015 International meeting on the molecular biology of hepatitis B viruses, Bad Nauheim, Germany, Oct. 3-8, 2015, 2015 - 長波長蛍光標識RNAプローブを用いたC型肝炎ウイルスNS3 helicaseの新規な活性測定手法
古田 篤史; Salam Kazi Abdus; 秋光 信佳; 田中 淳一; 山下 篤哉; 森石 恆司; 中越 雅道; 津吹 政可; 谷 英典; 常田 聡; 野田 尚宏, 日本生物工学会大会講演要旨集, 平成25年度, 162, 162, Aug. 2013
(公社)日本生物工学会, Japanese - Probe Electrospray Ionization質量分析法(PESI-MS)を用いたHCV感染細胞内脂質組成の解析
葛西宏威; 吉村健太郎; 安本順; 山下篤哉; 田中智久; 竹田扇; 森石恆司, 日本ウイルス学会学術集会プログラム・抄録集, 61st, 2013 - 海洋生物抽出物より取得した複数種の硫酸化合物によるC型肝炎ウイルスNS3 helicase阻害作用
古田 篤史; Kazi Abdus Salam; 秋光 信佳; 田中 淳一; 山下 篤哉; 森石 恆司; 中越 雅道; 津吹 政可; 谷 英典; 関口 勇地; 常田 聡; 野田 尚宏, 日本生物工学会大会講演要旨集, 平成24年度, 145, 145, Sep. 2012
(公社)日本生物工学会, Japanese - 海洋生物抽出物より取得したcholesterol sulfateによるC型肝炎ウイルスNS3 helicase阻害作用
古田 篤史; Salam Kazi Abdus; 長浜 夏樹; 秋光 信佳; 田中 淳一; 谷 英典; 山下 篤哉; 森石 恆司; 常田 聡; 関口 勇地; 野田 尚宏, 日本生物工学会大会講演要旨集, 平成23年度, 124, 124, Aug. 2011
(公社)日本生物工学会, Japanese - ELIMINATION OF HCV FROM HUMAN HEPATOCYTES BY INDUCTION OF TYPE I IFN VIA EXPRESSION OF IRF7
Xiaoyu Wen; Takayuki Abe; Kohji Moriishi; Yoshiharu Matsuura, JOURNAL OF GENE MEDICINE, 11, 12, 1165, 1166, Dec. 2009
English, Summary international conference - Identification of host factors required for HCV replication and possibility for development of anti-viral agents
森 嘉生; 森石 恆司; 松浦 善治, Cell technology., 27, 12, 1226, 1231, Dec. 2008
秀潤社, Japanese - Baculovirus vector for gene delivery and vaccine development
Hideki Tani; Takayuki Abe; Tomoko M. Matsunaga; Kohji Moriishi; Yoshiharu Matsuura, Future Virology, 3, 1, 35, 43, Jan. 2008
English, Book review - Hepatitis C virus RNA replication is regulated by FKBP8 and Hsp90 (vol 25, pg 5015, 2006)
Toru Okamoto; Yorihiro Nishimura; Tohru Ichimura; Kensuke Suzuki; Tatsuo Miyamura; Tetsuro Suzuki; Kohji Moriishi; Yoshiharu Matsuura, EMBO JOURNAL, 25, 23, 5634, 5634, Nov. 2006
English, Others - Hepatitis C virus and carcinogenesis
MORIISHI Kohji; MATSUURA Yoshiharu, 臨床とウイルス, 33, 5, 330, 335, 31 Dec. 2005
Japanese - HCVエンベロープ蛋白質を被ったシュードタイプVSVの感染機構
谷英樹; 菰田泰正; 山下哲生; 鈴木健介; 松尾栄子; 浜本いつき; 津田祥美; 林昌宏; 森石恆司; 考藤達哉; 林紀夫; 宮村達男; 松浦善治, 日本ウイルス学会学術集会プログラム・抄録集, 53rd, 97, 01 Nov. 2005
Japanese - 【ワクチンの免疫効果の増強法と誘導免疫の特性】 ワクチンベクターとしてのバキュロウイルス
阿部 隆之; 谷 英樹; 松永 朋子; 林 昌宏; 宮本 大伸; 森 嘉生; 森石 恆司; 松浦 善治, 臨床免疫, 43, 6, 652, 658, Jun. 2005
(有)科学評論社, Japanese - ヒト肝癌由来細胞で作製したHCV様粒子の性状
松尾栄子; 林昌宏; 菰田泰正; 森石恆司; 八木慎太郎; 松浦善治, 日本ウイルス学会学術集会プログラム・抄録集, 52nd, 206, 01 Nov. 2004
Japanese - 【ウイルス性肝炎 基礎・臨床研究の進歩】 C型肝炎ウイルス(HCV) HCVのレセプター候補分子
森石 恆司; 林 昌宏; 松浦 善治, 日本臨床, 62, 増刊7 ウイルス性肝炎(上), 191, 194, Jul. 2004
(株)日本臨床社, Japanese - 【ウイルスベクター 最新の話題】 バキュロウイルスベクター 哺乳動物細胞への遺伝子導入
谷 英樹; 阿部 隆之; 林 昌宏; 望月 理加; 山岸 潤也; 北川 善紀; 渡辺 理恵; 宮本 大伸; 森石 恆司; 松浦 善治, ウイルス, 53, 2, 185, 193, Dec. 2003
日本ウイルス学会, Japanese - 【肝疾患の分子生物学 治療への応用】 C型肝炎 C型肝炎ウイルス感染の分子機構と臨床への応用
鈴木 健介; 林 昌宏; 菰田 泰正; 森石 恆司; 松浦 善治, 最新医学, 58, 9, 2017, 2022, Sep. 2003
著者等はHCVの感染機構をin vitroで評価するため,HCVエンベロープタンパク質による細胞融合アッセイ系とエンベロープタンパク質を被ったシュードタイプウイルスを作製した.その結果,HCVの2つのエンベロープタンパク質が細胞表面のタンパク質受容体を認識し,エンドサイトーシスによって細胞内へ侵入することが示唆された.更に,HCVのエンベロープタンパク質のCD81との結合や細胞融合活性を阻害できるヒト型抗HCVエンベロープ抗体を得ることができた, (株)最新医学社, Japanese
- シンプル微生物学
南江堂, 05 Mar. 2018, 9784524254835, Japanese, Textbook, [Others] - 人獣共通感染症（改訂三版）
木村哲; 喜田宏, -
医薬ジャーナル, 01 Feb. 2016, 141-144, Japanese
- Regulatory mechanism of polycomb suppressive complex 1 activity by HCV infection
葛西宏威; 山下篤哉; 田中智久; 赤池康範; 大津直樹; 森石恆司
第68回 日本ウイルス学会総会, 16 Nov. 2021, Japanese, Oral presentation
神戸市, [Domestic Conference] - Cross-species transmission of rat hepacivirus and its adaptation to mouse.
大津直樹; 田中智久; 山下篤哉; 葛西宏威; 赤池康範; 森石恆司
第68回 日本ウイルス学会総会, 16 Nov. 2021, Japanese, Oral presentation
[Domestic Conference] - Identification of antiviral agents targeting HBV Enhancer I-X promoter
山下篤哉; 葛西宏威; 田中智久; 大津直樹; 赤池康範; 森石恆司
第68回 日本ウイルス学会総会, 16 Nov. 2021, Japanese
神戸市 - Transient and stable replicon systems of SARS-CoV-2 for drug screening
田中智久; 岡本徹; 葛西宏威; 山下篤哉; 森石恆司
第68回 日本ウイルス学会総会, 16 Nov. 2021, Japanese, Oral presentation
神戸市, [Domestic Conference] - HCV infection impairs monoubiquitination of histone H2A via proteolysis of RNF2 and activates expression of HOX genes
Hirotake Kasai; Kazuki Mochizuki; Tomohisa Tanaka; Atsuya Yamashita; Yoshiharu Matsuura; Kohji Moriishi
19th Awaji International Forum on Infection and Immunity, 28 Sep. 2021, English, Poster presentation
Sapporo, [International presentation] - Establishment of HepG2-derived cell line that permits HBV and HCV coinfection
Tomohisa Tanaka; Teruhime Otoguro; Takasuke Fukuhara; Moto Fukai; Akinobu Taketomi; Yoshiharu Matsuura; Kohji Moriishi
27th International meeting on hepatitis C virus and related viruses, 07 Jul. 2021, English, Oral presentation
Toronto, Canada(Hybrid), [International presentation] - Establishment of a novel cell culture model permissive for infection by hepatitis B and C viruses
Kohji Moriishi
Advanced Seminar Series on Microbiology and Immunology, 06 Jul. 2021, Japanese, Public discourse
大阪府吹田市, [Invited], [Domestic Conference] - B型肝炎ウイルス受容体結合領域に対する感染中和抗体の作製とエピトープ解析
矢藤慶悟; 小野寺大志; 松田麻未; 藤本陽; 渡士幸一; 相崎英樹; 加藤孝宣; 森石恆司; 田村浩二; 高橋宜聖; 脇田隆字; 村松正道; 鈴木亮介
第42回 日本分子生物学会総会, 03 Dec. 2019, Japanese, Poster presentation
福岡, [Domestic Conference] - 4,4'-bis(cyclohexylmethyl)biphenyl-2,2',5,5'-tetraol is the novel anti-HBV compound targeting the viral core promoter
Atsuya Yamashita; Tomohisa Tanaka; Teruhime Otoguro; Hirotake Kasai; Kohji Moriishi
67th Annual meeting of the Japanese Society for Virology, 29 Oct. 2019, English, Poster presentation
東京, [Domestic Conference] - Establishment of the cell line permissive for HBV and HCV coinfection
Teruhime Otoguro; Tomohisa Tanaka; Hirotake Kasai; Atsuya Yamashita; Takasuke Fukuhara; Yoshiharu Matsuura; Kohji Moriishi
67th Annual meeting of the Japanese Society for Virology, 29 Oct. 2019, English, Oral presentation
東京, [Domestic Conference] - Induction of HOX genes by HCV infection via a reduction in histone H2A monoubiquitination
Hirotake Kasai; Kohji Moriishi
26th International symposium on hepatitis C virus and related viruses, 20 Oct. 2019, English, Poster presentation
Soul, South Korea, [International presentation] - Involvement of a novel cyclin-dependent kinase in HBV infection
Tomohisa Tanaka; Kohji Moriishi
2019 International HBV Meeting, 03 Oct. 2019, English, Poster presentation
Melbourne, Australia, [International presentation] - Characterization of monoclonal antibodies against hepatitis B virus preS1 region from antigen-specific memory B cells
Keigo Yato; Taishi Onodera; Mami Matsuda; Akira Fujimoto; Koichi Watashi; Hideki Aizaki; Takanobu Kato; Kohji Moriishi; Koji Tamura; Yoshimasa Takahashi; Takaji Wakita; Masamichi Muramatsu; Ryosuke Suzuki
2019 International HBV Meeting, 03 Oct. 2019, English, Poster presentation
Melbourne, Australia, [International presentation] - B型およびC型肝炎ウイルスに近縁なウイルスとその由来
森石恆司
日本ウイルス学会 札幌支部会, 20 Jul. 2019, Japanese, Nominated symposium
札幌, [Invited], [Domestic Conference] - Inhibition of signal peptide peptidase restores monoubiquitination of histone H2A and impairs Hox gene expression in HCV-infected cells
Hirotake Kasai; Tomohisa Tanaka; Teruhime Otoguro; Atsuya Yamashita; Kohji Moriishi
第66回日本ウイルス学会学術集会, 28 Oct. 2018, English
[Domestic Conference] - Identification of Hepacivirus F subspecies from Japanese rodents
Tomohisa Tanaka; Teruhime Otoguro; Hirotake Kasai; Atsuya Yamashita; Hiroaki Kariwa; Kohji Moriishi
第66回日本ウイルス学会学術集会, 28 Oct. 2018, English, Poster presentation
[Domestic Conference] - Berberine suppresses hepatitis B virus production via impairment of HBV core promoter activity
Atsuya Yamashita; Tomohisa Tanaka; Teruhime Otoguro; Hirotake Kasai; Kohji Moriishi
第66回日本ウイルス学会学術集会, 28 Oct. 2018, English, Poster presentation
[Domestic Conference] - Inhibition of signal peptide peptidase restores monoubiquitination of histone H2A and impairs Hox gene expression in HCV-infected cells.
Hirotake Kasai; Tomohisa Tanaka; Atsuya Yamashita; Teruhime Otoguro; Kohji Moriishi
66th Annual meeting of the Japanese Society for Virology, 28 Oct. 2018, English, Oral presentation
Kyoto, Japan, [Domestic Conference] - Functional Characterization of hepacivirus replication
Moriishi Kohji
2018 USA-Japan hepatitis panel meeting, 27 Oct. 2018, English, Oral presentation
[Invited], [International presentation] - Identification of hepacivirus F subspecies in Japan
Tomohisa Tanaka; Hiroaki Kariwa; Kohji Moriishi
25th International symposium on hepatitis C virus and related viruses, 08 Oct. 2018, English, Poster presentation
[International presentation] - Identification of a cyclin-dependent kinase that facilitates HBV infection
Tomohisa Tanaka; Teruhime Otoguro; Hirotake Kasai; Atsuya Yamashita; Kohji Moriishi
International HBV Meeting, 03 Oct. 2018, English, Poster presentation
[International presentation] - BerberineのHBV増殖抑制活性とその抑制機序の解明
山下篤哉; 田中智久; 葛西宏威; 乙黒光姫; 梁明秀; 前川伸哉; 榎本信幸; 森石恆司
第28回抗ウイルス療法学会, 09 Jun. 2018, Japanese, Oral presentation
[Domestic Conference] - BerberineのHBV増殖抑制活性とその抑制機序の解明
山下篤哉; 田中智久; 葛西宏威; 乙黒光姫; 梁明秀; 前川伸哉; 榎本信幸; 森石恆司
第28回抗ウイルス療法学会学術集会, 07 Jun. 2018, Japanese
[Domestic Conference] - Functional Characterization of Hepacivirus Replication
Moriishi Kohji
International Symposium. BIOMARKERS FOR PERSONALIZED HEPATOLOGY, 30 May 2018, English, Oral presentation
[Invited], [International presentation] - 1. The bidirectional interplay of hepatitis B virus and cell-death inducing DFF45-like effectors
Hirotake Kasai; Jun Yasumoto; Atsuya Yamashita; Tomohisa Tanaka; Koichi Watashi; Takaji Wakita; Teruhime Otoguro; Kohji Moriishi
65th Annual Meeting of the Japanese Society for Virology, 24 Oct. 2017, English, Oral presentation
Osaka, [Domestic Conference] - Establishment of hepatitis B and C virus co-infection cell line
Teruhime Otoguro; Tomohisa Tanaka; Hirotake Kasai; Atsuya Yamashita; Kohji Moriishi
65th Annual Meeting of the Japanese Society for Virology, 24 Oct. 2017, English, Poster presentation
Osaka, [Domestic Conference] - Inhibitory effects of metachromin A on hepatitis B virus production via impairment of the viral promoter activity
Atsuya Yamashita; Tomohisa Tanaka; Teruhime Otoguro; Hirotake Kasai; Kohji Moriishi
65th Annual Meeting of the Japanese Society for Virology, 24 Oct. 2017, Japanese, Poster presentation
Osaka, [Domestic Conference] - 5’-terminal stem-loop of equine hepacivirus RNA permits miR-122-independent replication
Tomohisa Takana; Teruhime Otoguro; Hirotake Kasai; Atsuya Yamashita; Kohji Moriishi
65th Annual Meeting of the Japanese Society for Virology, 24 Oct. 2017, English, Oral presentation
Osaka, [Domestic Conference] - Screening of antiviral compounds using a highly HBV-permissible HpeG2 cell line
Tomohisa Tanaka; Teruhime Otoguro; Wenjia Chen; Hirotake Kasai; Atsuya Yamashita; Kohji Moriishi
2017 International meeting on Molecular Biology of Hepatitis B virus, 03 Sep. 2017, English, Poster presentation
Washington, D. C., USA, [International presentation] - Involvement of cell death inducing DFF45-like effectors in hepatitis B virus replication
Kohji Moriishi; Jun Yasumoto; Hirotake Kasai; Teruhime Otoguro; Atsuya Yamashita; Tomohisa Tanaka
2017 International meeting on Molecular Biology of Hepatitis B virus, 03 Sep. 2017, English, Poster presentation
Washington DC, USA, [International presentation] - CDK9 inhibitor FIT-039 suppresses HBV propagation.
Moriishi K; Tanaka T; Okuyama-Dobashi K; Chen W; Okamoto T; Ueda K; Hosaya T; Matsuura Y; Ryo A; Tanaka Y; Hagiwara M
第64回日本ウイルス学会総会, 24 Oct. 2016, Japanese, Oral presentation
札幌 - Anti-HBV activity of Coptidis rhizome alkaloids via targeting the viral core promoter.
Yamashita A; Tanaka T; Okuyama-Dobashi K; Kasai H; Moriishi K
Japanese Society for Virology, 24 Oct. 2016, 日本ウイルス学会, English, Oral presentation
札幌, [Domestic Conference] - Establishment of highly HBV-permissible HepG2 cell line to facilitate screening of antiviral compounds
Otoguro T; Tanaka T; Chen W; Kasai H; Yamashita A; Okuyama-Dobashi K; Moriishi K
第64回日本ウイルス学会総会, 24 Oct. 2016, English, Oral presentation
札幌 - Cross-species compatibility of hepacivirus 5’ untranslated region
Tanaka T; Otoguro T; Kasai H; Yamashita A; Okuyama-Dobashi K; Moriishi K
第64回日本ウイルス学会総会, 24 Oct. 2016, English, Nominated symposium
札幌, [International presentation] - Hepatitis C virus infection impairs mono-ubiquitination of histone H2A and activates expression of homeobox genes.
Hepatitis C virus; infection impairs mono-ubiquitination of; histone H2A; activates expression of; homeobox genes
第64回日本ウイルス学会総会, 24 Oct. 2016, English, Nominated symposium
[Domestic Conference] - Functional homology of hepacivirus 5’ UTRs in IRES activity and replication.
Tanaka T; Otoguro T; Kasai H; Yamashita A; Okuyama-Dobashi K; Moriishi K
23rd International symposium on hepatitis C virus and related viruses, 11 Oct. 2016, English, Poster presentation
Kyoto, Japan, [International presentation] - Inhibition of HBV propagation by treatment with CDK9 inhibitor FIT-039
Tanaka T; Okuyama-Dobashi K; Chen W; Okamoto T; Ueda K; Hosaya T; Matsuura Y; Ryo A; Tanaka Y; Hagiwara M; Kohji Moriishi
2016 Internationa HBV meeting, 21 Sep. 2016, English, Poster presentation
Yosei, Korea, [International presentation]
■ Research Themes
- ウイルス-人体相互作用ネットワークの理解と制御
ムーンショット型研究開発事業
Dec. 2020 - Nov. 2025
森石 恆司
国立研究開発法人科学技術振興機構, ウイルス-人体相互作用ネットワークの理解と操作, 山梨大学, Coinvestigator - History of humans and pathogens revealed by ancient viral genome analysis
Grants-in-Aid for Scientific Research
30 Jun. 2022 - 31 Mar. 2025
安達 登; 田中 智久; 神澤 秀明; 森石 恆司
青森県尻労安部遺跡および北海道北黄金貝塚から出土した人骨から検出されたヒトB型肝炎ウイルス(HBV)の遺伝子(以下、SHTおよびKGN)は、全領域を通じて塩基配列の相同性が高く、共通の祖先を持つHBV遺伝子と考えられた。既知のHBVのジェノタイプの中で、SHTとKGNはともに全体として東南アジア型のHBV遺伝子(SEA)に最も近ことが分かった。SHTもKGNも少なくともCore領域はSEA由来であり、SHTはSEA由来のS領域の一部を持っている。SHTはこのS領域において、ジェノタイプJやジェノタイプC4に非常に近い。そして、SHTとKGNの縄文タイプ（縄文タイプ：preS1に33bpのインサートを持ちその他の配列は全体としてSEAと近い）を系統ネットワーク解析した結果、これらのHBVは早い時期（：後期更新世の間）にSEAから分岐した可能性が示唆された。この結果から、SHTとKGNの共通祖先は東南アジアに起源を持ち、SEAから分岐して日本列島に到達し、そこで分岐・拡散したと考えられた。SEAには存在しないpreS1領域での33bpのインサートがSHT、KGNにはあることからも、SHTとKGNの縄文型はしばらくの間単系統であり、その後SHTとKGNに分岐した可能性があることが分かった。今回の研究で、東アジアに到達した初期の人類のうち、縄文人の祖先集団の一部とヒマラヤの南下集団との間に強い関係があることが明らかとなった。この成果を、第77回日本人類学会大会にて発表した。
Japan Society for the Promotion of Science, Grant-in-Aid for Challenging Research (Exploratory), University of Yamanashi, 22K19343 - Development of a research platform investing diagnostic, preventative, and therapeutic strategies for variant SARS-CoV-2
新興・再興感染症に対する革新的医薬品等開発推進研究事業
30 Oct. 2021 - 31 Mar. 2022
豊嶋 崇徳
本研究開発は、北海道と東北が連携して、変異を続ける新型コロナウイルスSARS-CoV-2感染者からの検体収集プラットフォームを構築するとともに、それら検体を用いて国際的にもトップの全国の研究者が協働し、当該ウイルスの新規診断・予防・治療法の研究開発プラットフォームを構築し、当該感染症を制圧し、将来の新たな新興感染症に対する基盤の整備を目的とする。
AMED, 101 新型コロナウイルス感染症の克服及び今後新たに発生する感染症対策のための基盤整備事業（新興・再興感染症データバンク事業）等を活用した研究, Competitive research funding - Basic research and development of novel diagnostic and therapeutic approaches for viral hepatitis
日本医療研究開発機構
01 Apr. 2021 - 31 Mar. 2022
Masamichi Muramatsu
肝炎等克服実用化研究事業, 肝炎等克服実用化研究事業, Competitive research funding - 肝炎ウイルスの感染複製増殖と病原性発現を阻止するための基盤的研究とその応用のための基盤的開発
肝炎等克服実用化研究事業・肝炎等克服緊急対策研究事業
Apr. 2019 - Mar. 2022
森石 恆司
国立研究開発法人日本医療研究開発機構, 山梨大学, Coinvestigator - 新規メカニズムに基づくB型肝炎治療薬の探索
肝炎等克服実用化研究事業・Ｂ型肝炎創薬実用化等研究事業
Apr. 2017 - Mar. 2022
森石 恆司
国立研究開発法人日本医療研究開発機構, 山梨大学, Coinvestigator - B型肝炎ウイルス（HBV）感染サイクル（生活環）で機能する宿主・ウイルス因子を標的とした新規抗HBV剤・HBV感染制御法の開発
肝炎等克服実用化研究事業・Ｂ型肝炎創薬実用化等研究事業
Apr. 2017 - Mar. 2022
森石 恆司
国立研究開発法人日本医療研究開発機構, 山梨大学, Coinvestigator - メカニズムに基づく抗SARS-CoV-2薬の創薬を目指した研究
新興・再興感染症に対する革新的医薬品等開発推進研究事業
01 Nov. 2020 - 31 Mar. 2021
松浦善治
AMED, 新興・再興感染症に対する革新的医薬品等開発推進研究事業, Competitive research funding - ウイルス-人体相互作用ネットワークの理解と制御 （慢性肝炎原因のウイルスモデル作製とネットワーク解析）
ムーンショット
01 Nov. 2020 - 31 Mar. 2021
松浦善治
内閣府 日本学術新興機構, ムーンショット 「2050年までに、超早期に疾患の予測・予防をすることができる社会を実現」目標２, Competitive research funding - Basic research and development of novel diagnostic and therapeutic approaches for viral hepatitis
日本医療研究開発機構
01 Apr. 2020 - 31 Mar. 2021
Masamichi Muramatsu
肝炎等克服実用化研究事業, 肝炎等克服実用化研究事業, Competitive research funding - B型肝炎ウイルス（HBV）感染サイクル（生活環）で機能する宿主・ウイルス因子を標的とした新規抗HBV剤・HBV感染制御法の開発
Ｂ型肝炎創薬実用化等研究事業
01 Apr. 2020 - 31 Mar. 2021
国立研究開発法人日本医療研究開発機構, 2017年度肝炎等克服実用化研究事業（Ｂ型肝炎創薬実用化等研究事業）, Competitive research funding - 2020年度 ／ 令和2年度 「新興・再興感染症に対する革新的医薬品等開発推進研究事業（新型コロナウイルス感染症（COVID-19）に対する研究）」に係る公募（5次公募）（課題公募番号101、201、301）について
日本医療研究開発機構研究費・新興・再興感染症に対する革新的医薬品等開発推進研究事業
Oct. 2020 - Mar. 2021
森石 恆司
国立研究開発法人日本医療研究開発機構, メカニズムに基づくSARS-CoV-2創薬を目指した基礎および非臨床研究, 山梨大学, Coinvestigator - Basic research and development of novel diagnostic and therapeutic approaches for viral hepatitis
日本医療研究開発機構
01 Apr. 2019 - 31 Mar. 2020
Masamichi Muramatsu
肝炎等克服実用化研究事業, 肝炎等克服実用化研究事業, Competitive research funding - B型肝炎ウイルス（HBV）感染サイクル（生活環）で機能する宿主・ウイルス因子を標的とした新規抗HBV剤・HBV感染制御法の開発
感染症実用化研究事業
01 Apr. 2017 - 31 Mar. 2018
上田啓次
AMED, 肝炎等克服実用化研究事業 B型肝炎創薬実用化等研究事業, Competitive research funding - プロテオミクスに基づく新規の抗肝炎ウイルス戦略
01 Apr. 2016 - 31 Mar. 2017
Competitive research funding - B型肝炎ウイルス感染受容体の分離・同定と感染系の樹立及び感染系による病態機構の解析と新規抗HBV剤の開発
01 Apr. 2016 - 31 Mar. 2017
AMED, Competitive research funding - B型肝炎ウイルスの完全排除等、完治を目指した新規治療法の開発に関する包括的研究
01 Apr. 2016 - 31 Mar. 2017
AMED, Competitive research funding - Search for antiviral molecules from coral reef organisms
Grants-in-Aid for Scientific Research
01 Apr. 2014 - 31 Mar. 2017
TANAKA Junichi; NODA Naohiro; SEKIGUCHI Yuji; TANI Hidenori; MORIISHI Kohji; YAMASHITA Atsuya; TSUNEDA Satoshi; AKIMITSU Nobuyoshi; TSUBUKI Masayoshi; FUJITA Yoshihisa; HIGASHI Masahiro
We constructed a library of extracts from coral reef organisms and a small library of marine natural products. They were screened for antiviral assays: HCV NS3 helicase, HCV replicon, and HBV core promoter. Some of hit extracts were separated and isolated compounds were characterized mainly by spectroscopic methods. After identifying hit molecules, we searched similar molecules and prepared derivatives by chemical transformations. The isolated compounds and derivatives were subjected for assays to see structure-activity relationship. We reported some of the results as papers or presentations in scientific meetings, though some of the contents are still under investigation.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), University of the Ryukyus, 26350973 - Discovery and development of agents for chronic hepatitis C from marine natural products
Grants-in-Aid for Scientific Research
01 Apr. 2013 - 31 Mar. 2016
YAMASHITA Atsuya; ENOMOTO Nobuyuki; MORIISHI Koji
We focused on pharmacologically active component from marine organisms for the development of novel anti hepatitis C virus agent. Thus, we screened extracts of marine organisms by using HCV replicon system and showed that the extract from Amphimedon sp. inhibits HCV replication by suppressing viral helicase and protease activities. In this study, we attempted to purify and identify the active component of Amphimedon sp., but not purify and identify it. Additionally, we established a cell-based screening system in order to identify compounds inhibiting the HCV NS2/3 protease activity. We screened extracts of marine organisms by using this system, but not identify extracts of marine organisms inhibiting the HCV NS2/3 protease activity.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), University of Yamanashi, 25460985 - Functions of p63 exoressed in hepatocellular carcinoma: DNA damage responses and relation to virus-induced carcinogenesis
Grants-in-Aid for Scientific Research
01 Apr. 2013 - 31 Mar. 2016
KATOH Iyoko; MORIISHI Kohji; KURATA Shun-ichi
This study investigated physical and functional interactions between p63, a member of the tumor suppressor p53 gene family, and hepatitis virus -related factors to detect the possible involvement of p63 in hepatocellular carcinogenesis. Interestingly, most of the hepatocellular carcinoma lines tested efficiently expressed the TA isoforms of p63 (TAp63) corresponding to p53. However, TAp63 did not respond to drug-induced DNA damage. No significant molecular interaction was evident between p63 and virus-related factors. Importantly, both HBV and HCV are known to activate the Wnt/beta-catenin signal transduction leading to carcinogenesis and malignancy. Our results showed interference of the Wnt-induced transcriptional activation by DeltaNp63alpha, indicating that hepatocellular carcinogenesis could be suppressed if the DeltaN isoform is expressed.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), University of Yamanashi, 25460475 - Infection of hepatitis C virus-related non-primate hepacivirus in Japan and analysis on its replication mechanism
Grants-in-Aid for Scientific Research
01 Apr. 2012 - 31 Mar. 2014
MORIISHI Kohji; YAMASHITA Atsuya; KASAI Hirotake
The objective of this study is to clarify if non-primate hepacivirus (NPHV) infects dogs or other animals in Japan. NPHV has been recently reported as a close homologue of hepatitis C virus (HCV). We prepared nose swabs from 11 dogs but did not find NPHV gene in those samples by RT-PCR. We also attempted to identify the virus from Japanese-born horses. Sera were prepared from 30 horses and were subjected to genetic analyses using RT-PCR. We identified equine hepacivirus (EHcV) in 30% preparations and determined a whole genome sequence. Non-translated regions and closed regions exhibit a similar structure to those of HCV, although 3'untranslated region of EHcV had not been reported. These results suggest that EHcV infects Japanese-born horses at a high rate in Japan compared to other countries.
Japan Society for the Promotion of Science, Grant-in-Aid for Challenging Exploratory Research, University of Yamanashi, 24659204 - Study on proteasome-dependent regulation of viral infection
Grants-in-Aid for Scientific Research
2009 - 2011
MORIISHI Kohji
It has been unknown the mechanism by which ubiquitin-independent proteasome regulates hepatitis C virus(HCV) infection. HCV propagation was suppressed by inhibition of ubiquitin-independent proteasome in cell culture system. Furthermore, ubiquitin-independent proteasome associated with cell proliferation and DNA repair in the liver of mouse model. These data suggest that ubiquitin-independent proteasome plays an important role in HCV infection and pathogenicity.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), 21590508 - Study on the lipid biosynthesis and the related phathology in. hepatitis C virus infection
Grants-in-Aid for Scientific Research
2007 - 2008
MORIISHI Koji; MORIISHI Koji
C型肝炎ウイルス(HCV)コア蛋白質は、細胞内のラフト様構造にも局在してるが、ウイルス感染環あるいは病原性における役割はわかっていない。本研究によって、膜内切断を受けたコア蛋白質はウイルス粒子形成に必要であることが示された。また、コア蛋白質とPA28γの発現によって脂質代謝が増強される現象は、インターフェロン抵抗性を示すC型肝炎患者で多く認められるコア蛋白質変異によって減弱していた。以上のことから、コア蛋白質を修飾する宿主蛋白質を標的にした薬剤が、抗HCV薬として期待出来ることが分かった
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Osaka University, 19590473 - Effect of host proteasome on Hepatitis C virus infection
Grants-in-Aid for Scientific Research
2004 - 2005
MORIISHI Kohji
The third place of cancer death in our country is liver cancer, of which eighty percentage patients are infected with hepatitis C virus (HCV). HCV core protein is well known to be the capsid protein as well as the pathogenic factor, because liver cancer and steatosis are found in HCV core protein-transgenic mouse. The aims of our study are to clarify the mechanism by which HCV core protein induces pathogenicity and to understand how HCV core protein is processed by host protein.
1)Effect of PA28gamma on processing and pathogenicity of HCV core protein.
Expression of PA28gamma was suppressed by short hairpin-typed RNA under the control of U6 promoter. Posttranslational and translational modifications of the proteins related to cell growth and lipid biosynthesis in PA28gamma-knockdown cells were different from those in parents cells. We also determine the region spanning from residues 139 to 144 as the essential domain for ER retention and the region from residues 176 to 177 as the SPP-processing essential region. In addition, our data also suggest that oligomerization of HCV core protein is important for E1 interaction.
2)Biological function of HCV core protein is regulated by SPP and PA28gamma
C-terminal transmembrane region of HCV core protein is processed by signal peptidase and then signal peptide peptidase. Analysis of MALDI-TOF/MS suggests that C-terminal amino acid residue is determined as residue 178. Our data also suggest that SPP processing affects intracellular localization of HCV core protein and that HCV core protein regulates the nuclear proteasome activity.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Osaka University, 16590385 - C型肝炎ウイルス感染による肝発癌に関与する宿主因子の同定とその作用機構
科学研究費助成事業
2004 - 2005
森石 恆司
肝癌は我が国の癌死の第3位を占め、その約8割がC型肝炎ウイルス(HCV)感染に起因している。HCVコア蛋白質を発現するマウスがヒトと似た経過で脂肪肝・肝癌を発症することから、HCVコア蛋白質の宿主細胞内での機能が注目されている。本研究では、HCVコア蛋白質の成熟過程と病原性発現機構の詳細を明らかにし、宿主蛋白質を標的とした新規治療法開発の基盤確立を目的としている。
1)HCVコア蛋白質による肝臓脂肪化および癌化におけるPA28γの意義
PA28γ(-/-)マウス、PA28γ(+/+)コアTgマウス、PA28γ(-/-)コアTgマウスおよびPA28γ(+/+)マウスの肝臓の脂肪化について観察した。PA28γ(+/+)コアTgマウスのみで肝臓の脂肪化が確認され、PA28γ欠損あるいはコア蛋白質非発現のマウスでは肝臓の脂肪化は観察されなかった。脂肪滴の蓄積の原因はトリグリセリド・脂肪酸の蓄積が考えれられることから、脂肪合成関連遺伝子の発現を解析し、特定の転写因子の活性化がマウスおよび培養細胞でコア蛋白質およびPA28γに依存して認められた。その上流域の転写因子の活性化も、コア蛋白質およびPA28γに依存して認められた。肝細胞癌に関してもPA28γノックアウトによって軽減された。
2)PA28γ遺伝子欠損・コア蛋白質発現による宿主内蛋白質発現の変化:PA28γ(+/+)コアTgマウス、PA28γ(-/-)コアTgマウスおよびPA28γ(+/+)マウス肝臓内蛋白質発現の違いを抗体アレイによって解析し、特定の蛋白質の発現に変化が認められた。
日本学術振興会, 特定領域研究, 大阪大学, 16017258 - Study on infection and maturation mechanisms of hepatitis C virus and its host response.
Grants-in-Aid for Scientific Research
2003 - 2005
MATSUURA Yoshiharu; MORIISHI Kohji
To examine the molecular mechanisms of hepatitis C virus (HCV) infection, we prepared pseudotype viruses bearing unmodified HCV envelope proteins based on vesicular stomatitis virus (HCVpv) in both 293T and CHO cells. HCVpv generated in 293T cells (HCVpv/293T) exhibited a high infectivity to Huh7 cells but not to HepG2 cells. The infection of HCVpv/293T to Huh7 cells was neutralized by anti-hCD81 antibody, as reported for the pseudotype viruses based on murine leukemia virus (HCVpp) generated in 293T cells. In contrast, HCVpv generated in CHO cells (HCVpv/CHO) exhibited a high infectivity to hCD81-negative HepG2 cells and a weak infectivity to Huh7 cells. These results indicate that HCVpv/293T and HCVpv/CHO exhibit hCD81-dependent and -independent infectivity, respectively. Sera taken from chronic hepatitis C patients efficiently neutralized HCVpv/293T infection, as reported for HCVpp infection, whereas only a slight inhibition of HCVpv/CHO infection was observed. Naturally occurring HCV particles in serum taken from a hepatitis C patient during the window period of infection also exhibited binding to both Huh7 and HepG2 cells. In conclusion, these results indicate that the cell tropism of the HCV pseudotype viruses is determined by the producing cell lines, and that at least two types of HCV particles bearing similar properties to the pseudotype viruses exhibiting hCD81-dependent and -independent infection circulate in the serum of hepatitis C patients.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (A), Osaka University, 15209017 - Study on infection mechanisms of hepatitis C virus
Grants-in-Aid for Scientific Research
2000 - 2002
MATSUURA Yoshiharu; MIYAZAWA Takayuki; MORIISHI Kohji
Studies of infection mechanisms of hepatitis C virus (HCV) have been hampered by the lack of conventional cell culture system which support replication of HCV. To overcome this problem, we have established a sensitive cell fusion assay system and also constructed pseudotype vesicular stomatitis virus (VSV) possessing HCV envelope protein on the surface of the virion instead of its own envelope G glycoprotein. The chimeric HCV E1 and E2 proteins consisting of the ectodomain of E1 or E2 envelope proteins and the transmembrane and cytoplasmic domains of VSV G glycoprotein were expressed on the cell surface. The induction of cell fusion requires both of the chimeric E1 and E2 proteins with low pH-dependent manner. The pseudotype virus possessing both of the chimeric E1 and E2 proteins exhibited significantly higher susceptibility than that possessing either of the glycoproteins individually. These results suggest that HCV requires both E1 and E2 proteins in the infection and enters a target cell via an endosomal pathway. In the endosome, a low pH-dependent conformation change of the E1 or/and E2 proteins occurs, which then triggers membrane fusion and the entry of the nucleocapsid into the cytoplasm. Treatment of HepG2 cells with pronase, heparinase, or heparitinase reduced the levels of cell fusion activity and infectivity of the pseudotype VSV suggesting that certain protein molecules and glycosaminoglycans on the cell surface play an important role in the infection with HCV. Recently, human CD81 (hCD81) has been shown to be a binding receptor of the E2 protein. However, there was no difference in cell fusion activity and susceptibility to pseudotype VSV between the mouse cell line expressing hCD81 and the parental cell line. These results suggest that hCD81 atone is not sufficient to allow infection of HCV and that another cofactor(s) might be required or that HCV infection may occur in an hCD81-independent manner.
The infection mechanisms revealed in this study might offer an important information for future studies on cellular receptors for HCV and for the development of prophylactics and therapeutics for hepatitis C.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Osaka University, 12470072 - ボツリヌスC1型神経毒素のアクセプターの一次構造と分子機構
科学研究費助成事業
1994 - 1994
森石 恆司
パニングによるボツリヌス神経毒素の標的細胞上のアクセプター分子の単離するために、1.毒素分子上の結合領域の大腸菌による発現、2.パニングによるアクセプター分子の単離の二段階で行うことにした。
1.毒素分子上の結合領域の大腸菌による発現
C1型毒素とD型毒素は結合する標的細胞上のアクセプター分子は異なると考えられ、その毒素分子結合領域は毒素分子上のC末端側に存在すると考えられている。毒素分子上の結合領域の位置を正確に把握すると共にその部分をクリアカットに単離するために、C1型およびD型毒素遺伝子を単離し、大腸菌で発現する試みを行った。C1型毒素遺伝子をC型6813株からPCRによって、八つの断片として単離し、全核酸配列を決定した。コードされるC1型毒素は1280個のアミノ酸で構成され、分子量147,814であった。また、D型毒素遺伝子をD型サウスアフリカ株の毒素伝達ファージのゲノムDNAから、プラスミドベクターを用いてクローニングした。そこにコードされるD型毒素は既に発表されているC型ストックホルム株とD型1873株の毒素とから構成されるキメラ毒素であることがわかった。結合領域はC末端に存在し、しかもC1型毒素とD型毒素と構造が異なることが予想される。したがって、それら毒素分子の比較分析からC末端380個以内にアクセプター結合領域が存在すると推定した。そのC末端380個と、その中でもさらに相同性低いC末端100個の領域をPCRによって増幅し、PLプロモーターによって発現するpTrxFusベクターに組み込み可溶化画分にチオレドキシン融合蛋白質として得た。その発現蛋白質の結合活性を各種神経芽細胞で検査中である。
2.パニングによるアクセプター分子の単離
NG108細胞からmRNAを単離し、それらcDNAを合成しベクターに組み込みCOS細胞で発現ライブラリーを作成した。抗チオレドキシン抗体をプレートに結合させ、発現融合蛋白質をその抗体に結合させ、結合細胞をクローニングしているところである。
日本学術振興会, 奨励研究(A), 国立予防衛生研究所, 06760270
■ Academic and Social Contribution Activities/Other
Social Contribution Activities
