Researcher Database

Hiroaki Kariwa
Faculty of Veterinary Medicine Veterinary Medicine Preventive Veterinary Medicine
Professor

Researcher Profile and Settings

Affiliation

  • Faculty of Veterinary Medicine Veterinary Medicine Preventive Veterinary Medicine

Job Title

  • Professor

Degree

  • Ph.D(Hokkaido University)

URL

J-Global ID

Research Interests

  • 人獣共通感染症   ウイルス学   公衆衛生学   Zoonosis   Virology   Public Health   

Research Areas

  • Life sciences / Veterinary medicine
  • Life sciences / Veterinary medicine
  • Life sciences / Veterinary medicine

Association Memberships

  • 人と動物の共通感染症研究会   獣医疫学会   日本ウイルス学会   日本獣医学会   日本獣医公衆衛生学会   The Japan Society of Veterinary Epidemiology   The Japanese Society for Virology   The Japanese Society of Veterinary Science   The Japanese Society of Veterinary Public Health   

Research Activities

Published Papers

  • Serological survey of severe fever with thrombocytopenia syndrome virus infection in Sika deer and rodents in Japan.
    Lundu T, Yoshii K, Kobayashi S, Morikawa S, Tsubota T, Misawa N, Hayasaka D, Kariwa H
    Japanese Journal of Veterinary Research 66 (1) 21 - 28 2018/02 [Refereed][Not invited]
  • Lundu T, Tsuda Y, Ito R, Shimizu K, Kobayashi S, Yoshii K, Yoshimatsu K, Arikawa J, Kariwa H
    Biomedical research (Tokyo, Japan) 39 (1) 27 - 38 0388-6107 2018/01 [Refereed][Not invited]
  • Ludek Eyer, Hirofumi Kondo, Darina Zouharova, Minato Hirano, James J. Valdes, Memi Muto, Tomas Kastl, Shintaro Kobayashi, Jan Haviernik, Manabu Igarashi, Hiroaki Kariwa, Marketa Vaculovicova, Jiri Cerny, Rene Kizek, Andrea Kroeger, Stefan Lienenklaus, Milan Dejmek, Radim Nencka, Martin Palus, Jiri Salat, Erik De Clercq, Kentaro Yoshii, Daniel Ruzek
    JOURNAL OF VIROLOGY 91 (21) 0022-538X 2017/11 [Refereed][Not invited]
     
    borne encephalitis virus (TBEV) causes a severe and potentially fatal neuroinfection in humans. Despite its high medical relevance, no specific antiviral therapy is currently available. Here we demonstrate that treatment with a nucleoside analog, 7-deaza-2'-C-methyladenosine (7-deaza-2'-CMA), substantially improved disease outcomes, increased survival, and reduced signs of neuroinfection and viral titers in the brains of mice infected with a lethal dose of TBEV. To investigate the mechanism of action of 7-deaza-2'-CMA, two drug-resistant TBEV clones were generated and characterized. The two clones shared a signature amino acid substitution, S603T, in the viral NS5 RNA-dependent RNA polymerase (RdRp) domain. This mutation conferred resistance to various 2'-C-methylated nucleoside derivatives, but no cross-resistance was seen with other nucleoside analogs, such as 4'-C-azidocytidine and 2'-deoxy-2'-beta-hydroxy-4'-azidocytidine (RO-9187). All-atom molecular dynamics simulations revealed that the S603T RdRp mutant repels a water molecule that coordinates the position of a metal ion cofactor as 2'-C-methylated nucleoside analogs approach the active site. To investigate its phenotype, the S603T mutation was introduced into a recombinant TBEV strain (Oshima-IC) generated from an infectious cDNA clone and into a TBEV replicon that expresses a reporter luciferase gene (Oshima-REP- luc2A). The mutants were replication impaired, showing reduced growth and a small plaque size in mammalian cell culture and reduced levels of neuroinvasiveness and neurovirulence in rodent models. These results indicate that TBEV resistance to 2'-C-methylated nucleoside inhibitors is conferred by a single conservative mutation that causes a subtle atomic effect within the active site of the viral NS5 RdRp and is associated with strong attenuation of the virus. IMPORTANCE This study found that the nucleoside analog 7-deaza-2'-C-methyl-adenosine (7-deaza-2'-CMA) has high antiviral activity against tick-borne encephalitis virus (TBEV), a pathogen that causes severe human neuroinfections in large areas of Europe and Asia and for which there is currently no specific therapy. Treating mice infected with a lethal dose of TBEV with 7-deaza-2'-CMA resulted in significantly higher survival rates and reduced the severity of neurological signs of the disease. Thus, this compound shows promise for further development as an anti-TBEV drug. It is important to generate drug-resistant mutants to understand how the drug works and to develop guidelines for patient treatment. We generated TBEV mutants that were resistant not only to 7-deaza-2'-CMA but also to a broad range of other 2'-C-methylated antiviral medications. Our findings suggest that combination therapy may be used to improve treatment and reduce the emergence of drug-resistant viruses during nucleoside analog therapy for TBEV infection.
  • Minato Hirano, Memi Muto, Mizuki Sakai, Hirofumi Kondo, Shintaro Kobayashi, Hiroaki Kariwa, Kentaro Yoshii
    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 114 (37) 9960 - 9965 0027-8424 2017/09 [Refereed][Not invited]
     
    Neurological diseases caused by encephalitic flaviviruses are severe and associated with high levels of mortality. However, little is known about the detailed mechanisms of viral replication and pathogenicity in the brain. Previously, we reported that the genomic RNA of tick-borne encephalitis virus (TBEV), a member of the genus Flavivirus, is transported and replicated in the dendrites of neurons. In the present study, we analyzed the transport mechanism of the viral genome to dendrites. We identified specific sequences of the 5' untranslated region of TBEV genomic RNA that act as a cis-acting element for RNA transport. Mutated TBEV with impaired RNA transport in dendrites caused a reduction in neurological symptoms in infected mice. We show that neuronal granules, which regulate the transport and local translation of dendritic mRNAs, are involved in TBEV genomic RNA transport. TBEV genomic RNA bound an RNA-binding protein of neuronal granules and disturbed the transport of dendritic mRNAs. These results demonstrated a neuropathogenic virus hijacking the neuronal granule system for the transport of viral genomic RNA in dendrites, resulting in severe neurological disease.
  • Shintaro Kobayashi, Kentaro Yoshii, Minato Hirano, Memi Muto, Hiroaki Kariwa
    JOURNAL OF VIROLOGICAL METHODS 240 14 - 20 0166-0934 2017/02 [Refereed][Not invited]
     
    Reverse genetics systems facilitate investigation of many aspects of the life cycle and pathogenesis of viruses. However, genetic instability in Escherichia coli has hampered development of a reverse genetics system for West Nile virus (WNV). In this study, we developed a novel reverse genetics system for WNV based on homologous recombination in mammalian cells. Introduction of the DNA fragment coding for the WNV structural protein together with a DNA-based replicon resulted in the release of infectious WNV. The growth rate and plague size of the recombinant virus were almost identical to those of the parent WNV. Furthermore, chimeric WNV was produced by introducing the DNA fragment coding for the structural protein and replicon plasmid derived from various strains. Here, we report development of a novel system that will facilitate research into WNV infection. (C) 2016 Elsevier B.V. All rights reserved.
  • Kariwa H
    Uirusu 67 (1) 25 - 32 0042-6857 2017 [Refereed][Not invited]

Books etc

  • Animal viruses
    Transworld Research Network 2010
  • SARS
    Transworld Research Network 2006
  • Hantaviruses and Hantavirus infections
    Times New Roman 2003

MISC

  • Hiroaki Kariwa, Haruka Yoshida, Cornelio Sanchez-Hernandez, Maria de Lourdes Romero-Almaraz, Jose Alberto Almazan-Catalan, Celso Ramos, Daisuke Miyashita, Takahiro Seto, Ayako Takano, Masashi Totani, Ryo Murata, Ngonda Saasa, Mariko Ishizuka, Takahiro Sanada, Kentaro Yoshii, Kumiko Yoshimatsu, Jiro Arikawa, Ikuo Takashima  VIRUS RESEARCH  163-  (2)  486  -494  2012/02  [Not refereed][Not invited]
     
    A variety of hantaviruses are harbored by rodents in North and South America, some of which can cause hantavirus pulmonary syndrome. To obtain greater evolutionary insight into hantaviruses in the Americas, a total of 211 rodents were captured in the Mexican states of Guerrero and Morelos in 2006. Anti-hantavirus antibodies were detected in 27 of 211 serum samples (12.8%) by ELISA. The distribution of seropositive rodents was: 17 Peromyscus beatae, 1 Megadontomys thomasi,1 Neotoma picta, 6 Reithrodontomys sumichrasti, and 2 Reithrodontomys megalotis. The hantavirus small (S), medium (M), and large (L) genome segments from P. beatae, R. sumichrasti, and R. megalotis were amplified and the sequences covering the open reading frames were determined. The hantaviruses from P. beatae, R. sumichrasti, and R. megalotis were provisionally designated Montano (MTN), Carrizal (CAR), and Huitzilac (HUI), respectively. The M segment amino acid identities among the Mexican hantaviruses were 80.8-93.0%. When these M segments were compared to those of known hantaviruses, MTN virus was most closely related to Limestone Canyon (LSC) virus (88.9% amino acid identity), while the CAR and HUI viruses were most closely related to El Moro Canyon (ELMC) virus (90-91% identity). Phylogenetic analysis revealed that the MTN, CAR, and HUI viruses occupy a monophyletic clade with the LSC, ELMC, and Rio Segundo viruses, which are harbored by Peromyscus boylii, R. megalotis, and Reithrodontomys mexicanus, respectively. The data obtained in this study provide important information for understanding the evolution of hantaviruses in the Americas. (C) 2011 Elsevier B.V. All rights reserved.
  • Takahiro Seto, Noriyo Nagata, Keisuke Yoshikawa, Osamu Ichii, Takahiro Sanada, Ngonda Saasa, Yuka Ozaki, Yasunori Kon, Kentaro Yoshii, Ikuo Takashima, Hiroaki Kariwa  VIRUS RESEARCH  163-  (1)  284  -290  2012/01  [Not refereed][Not invited]
     
    Hantaan virus (HTNV) is a causative agent of hemorrhagic fever with renal syndrome (HFRS). The pathogenesis of HFRS has not been fully elucidated, mainly due to the lack of a suitable animal model. In laboratory mice, HTNV causes encephalitis. However, that symptom is dissimilar to human hantavirus infections. We found that HTNV strain AA57 (isolated from Apodemus agrarius in Far East Russia) caused pulmonary disease in 2-week-old ICR mice. The clinical signs of the infected mice were piloerection, trembling, hunching, labored breathing, and body-weight loss. A large volume of pleural effusion was collected from thoracic cavities of the dead mice. Overall, 45% of the mice inoculated with 3000 focus forming units (FFU) of the virus began to show clinical symptoms at 8 days post-inoculation, and 25% of the inoculated mice died within 3 days of onset of the disease. The morbidity and mortality rates of the mice inoculated with 30-30,000 FFU of HTNV strain AA57 were roughly equivalent. The highest rates of virus positivity (11/12) and the highest titers of HTNV strain AA57 were detected in the lungs of the dead mice, while lower detection rates and viral titers were found in the heart, kidneys, spleen, and brain. Interstitial pneumonia, perivascular edema, hemorrhage, inflammatory infiltration and vascular failure were observed in the lungs of the sick mice. Hantaviral antigens were detected in the lung endothelial cells of the sick mice. The symptoms and pathology of this mouse model resemble those of hantavirus pulmonary syndrome (HPS) and, to a certain extent, those of HFRS. This is the first report that, in laboratory mice, the HFRS-related hantavirus causes a HPS-like disease and shares some symptom similarities with HFRS. (C) 2011 Elsevier B.V. All rights reserved.
  • Kentaro Yoshii, Manabu Igarashi, Osamu Ichii, Kana Yokozawa, Kimihito Ito, Hiroaki Kariwa, Ikuo Takashima  JOURNAL OF GENERAL VIROLOGY  93-  (1)  27  -38  2012/01  [Not refereed][Not invited]
     
    Flaviviruses are assembled to bud into the lumen of the endoplasmic reticulum (ER) and are secreted through the vesicle transport pathway, but the details of the molecular mechanism of virion assembly remain largely unknown. In this study, a highly conserved region in the prM protein was identified among flaviviruses. In the subviral particle (SP) system of tick-borne encephalitis virus (TBEV) and Japanese encephalitis virus, secretion of SPs was impaired by a mutation in the conserved region in the prM protein. Viral proteins were sparse in the Golgi complex and accumulated in the ER. Ultrastructural analysis revealed that long filamentous structures, rather than spherical SPs, were observed in the lumen of the ER as a result of the mutation. The production of infectious virions derived from infectious cDNA of TBEV was also reduced by mutations in the conserved region. Molecular modelling analysis suggested that the conserved region is important for the association of prM-envelope protein heterodimers in the formation of a spike of immature virion. These results are the first demonstration that the conserved region in the prM protein is a molecular determinant for the flavivirus assembly process.
  • Masashi Totani, Kentaro Yoshii, Hiroaki Kariwa, Ikuo Takashima  AVIAN DISEASES  55-  (4)  561  -568  2011/12  [Not refereed][Not invited]
     
    Birds are important for the transmission of West Nile virus (WNV) in nature, but the significance of the potential N-linked glycosylation at position 154 in the WNV envelope (E) protein with regard to viral replication in young chickens has not been assessed. In this study, the effect of glycosylation of the WNV E protein on viral pathogenicity in birds was investigated using young domestic chicks. A higher viral load was detected in the blood and the peripheral organs, particularly the hearts, of 2-day-old chicks inoculated with a glycosylated WNV variant compared to those inoculated with the nonglycosylated variant. There was no significant difference in the neutralizing antibody titers and cytokine expression profiles in chickens inoculated with the glycosylated and the nonglycosylated WNV variants. In contrast, no virus was detected in the blood and the tissues of 3-wk-old chicks, although the host immune response was induced to similar levels as in the 2-day-old chicks. These data indicate the utility of young domestic chicks as an animal model of WNV infection; they also indicate that glycosylation of the E protein of WNV enhances multiplication in the blood and peripheral organs, which is associated with the strong pathogenicity of WNV in birds.
  • Yuki Omori-Urabe, Kentaro Yoshii, Ayae Ikawa-Yoshida, Hiroaki Kariwa, Ikuo Takashima  MICROBIOLOGY AND IMMUNOLOGY  55-  (12)  893  -897  2011/12  [Not refereed][Not invited]
     
    Tick-borne encephalitis virus (TBEV) causes severe encephalitis in humans. It is endemic in one area of Japan; however no commercial vaccine is available in that country. In this Japan-based study, the efficacy of subviral particles (SPs) of TBEV administered by needle-free injector was evaluated as a vaccine candidate. Inoculation with SP-encoding DNA by needle-free injector induced neutralizing antibodies more efficiently than when administered by needle and syringe, and mice vaccinated with one dose by needle-free injector survived challenge with a lethal dose of TBEV. These results suggest that SP vaccines delivered by needle-free injector can protect against TBEV infection.
  • Ayako Takano, Kentaro Yoshii, Yuki Omori-Urabe, Kana Yokozawa, Hiroaki Kariwa, Ikuo Takashima  ARCHIVES OF VIROLOGY  156-  (11)  1931  -1941  2011/11  [Not refereed][Not invited]
     
    Tick-borne encephalitis virus (TBEV) causes severe encephalitis in humans. The Sofjin-HO strain is the prototype strain of the TBEV Far-Eastern subtype and is highly pathogenic in a mouse model. In this study, we constructed replicons and infectious cDNA clones of the Sofjin-HO strain. The replication of the replicon RNA was confirmed, and infectious viruses were recovered from the infectious cDNA clone. The recombinant viruses showed similar virulence characteristics to those of the parental virus. While characterizing the replicon and infectious cDNA, several amino acid differences derived from cell culture adaptations were analysed. The amino acids differences at E position 496 and NS4A position 58 were found to affect viral replication. The Gly- or Ala-to-Glu substitution at E position 122 was shown to increase neuroinvasiveness in mice. These replicons and infectious cDNA clones are useful in revealing the viral molecular determinants involved in the replication and pathogenicity of TBEV.
  • Takahiro Sanada, Hiroaki Kariwa, Noriyo Nagata, Yoichi Tanikawa, Takahiro Seto, Kumiko Yoshimatsu, Jiro Arikawa, Kentaro Yoshii, Ikuo Takashima  VIRUS RESEARCH  160-  (1-2)  108  -119  2011/09  [Not refereed][Not invited]
     
    The mechanism of hantavirus persistent infection in natural hosts is poorly understood due to a lack of laboratory animal models. Herein, we report that Syrian hamsters (Mesocricetus auratus) infected with Puumala virus (PUUV) at 4 weeks old show persistent infection without clinical symptoms for more than 2 months. IgG and IgM antibodies against the viral nucleocapsid protein and neutralizing antibody were first detectable at 14 days postinoculation (dpi) and maintained through 70 dpi. Viral RNA was first detected from 3 dpi in lungs and blood clots, and was detected in all tissues tested at 7 dpi. The viral RNA persisted for at least 70 days in the lungs, kidney, spleen, heart, and brain. The highest level of RNA copies was observed at 14 dpi in the lungs. Slight inflammatory reactions were observed in the lungs, adrenal glands, and brain. Immunohistochemical analysis revealed that PUUV antigen persisted until 56 dpi in the kidneys and adrenal glands. Infected hamsters showed no body weight loss or clinical signs. These results indicate that PUUV infection in hamsters is quite similar to the hantavirus infection of natural host rodents. (C) 2011 Elsevier B.V. All rights reserved.
  • Mayumi Obara, Takeo Yamauchi, Mamoru Watanabe, Sumiyo Hasegawa, Yasufumi Ueda, Kentaro Matsuno, Masae Iwai, Eiji Horimoto, Takeshi Kurata, Takenori Takizawa, Hiroaki Kariwa, Ikuo Takashima  AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE  84-  (5)  695  -708  2011/05  [Not refereed][Not invited]
     
    To determine the mechanisms of maintenance and evolution of Japanese encephalitis virus (JEV) in a temperate zone, we attempted to isolate JEV from mosquitoes and pigs in Toyama Prefecture, Japan. A total of 87 JEVs were isolated from female Culex tritaeniorhynchus mosquitoes and pigs during 2005-2009. The prevalence of JEV in Toyama Prefecture was seasonally late in comparison with that of the virus during 1966-1972. Furthermore, JEVs were isolated after the peak in the number of female Cx. tritaeniorhynchus. Among JEV strains isolated in this study, two distinct groups were observed within genotype I of the phylogeny generated from nucleotide sequence information derived from the envelope and capsid/premembrane genes: strains belonging to the major type were isolated during 2005-2009, and strains from the minor type were isolated only in 2007. The major type has exhibited gradual change in its envelope and capsid/premembrane genes, and all isolates obtained in 2008 and 2009 had a novel deletion of seven nucleotides in the variable region of the 3'-untranslated region.
  • Takahiro Seto, Evgeniy A. Tkachenko, Vyacheslav G. Morozov, Yoichi Tanikawa, Sergey I. Kolominov, Sergey N. Belov, Ichiro Nakamura, Nobuo Hashimoto, Yasuhiro Kon, Alexander E. Balakiev, Tamara K. Dzagurnova, Olga A. Medvedkina, Mina Nakauchi, Mariko Ishizuka, Kentaro Yoshii, Kumiko Yoshimatsu, Leonid V. Ivanov, Jiro Arikawa, Ikuo Takashima, Hiroaki Kariwa  JOURNAL OF VIROLOGICAL METHODS  173-  (1)  17  -23  2011/04  [Not refereed][Not invited]
     
    Puumala virus (PUUV) and other Arvicolinae-borne hantaviruses are difficult to cultivate in cell culture. To isolate these hantaviruses efficiently, hantavirus nucleocapsid protein (NP)-positive but seronegative wild rodents were selected by NP-detection ELISA. Three of 68 Myodes glareolus captured in Samara, Russia, were NP-positive and seronegative. Syrian hamsters were inoculated with lung homogenates from NP-positive rodents for virus propagation. Virus isolation in vitro was carried out by inoculation of lung homogenates of NP-positive hamsters to Vero E6 cell monolayers. Two PUUV strains (Samara49/CG/2005 and Samara94/CG/2005) from M. glareolus were isolated in Vero E6 cells. Nucleotide and amino acid sequence identities of the S segment of these isolates to those of PUUV F-s808 from a fatal HFRS patient in Samara region were 96.7-99.3% and 99.3-100.0%, respectively. Morphologic features of Vero E6 cells infected with PUUV strain Samara49/CG/2005 were quite similar to those of Hantaan virus-infected cells. Isolation of Hokkaido virus from Myodes rufocanus captured in Hokkaido, Japan, was also performed. Hokkaido virus NP and RNA were recovered and maintained in hamsters. These results suggest that inoculation of Syrian hamsters with rodent samples is an efficient method for the isolation and maintenance of PUUV and other Arvicolinae-borne hantaviruses. (C) 2011 Elsevier B.V. All rights reserved.
  • Ryo Murata, Kazuaki Hashiguchi, Kentaro Yoshii, Hiroaki Kariwa, Kensuke Nakajima, Leonid I. Ivanov, Galina N. Leonova, Ikuo Takashima  AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE  84-  (3)  461  -465  2011/03  [Not refereed][Not invited]
     
    West Nile (WN) virus has been spreading geographically to non-endemic areas in various parts of the world. However, little is known about the extent of WN virus infection in Russia. Japanese encephalitis (JE) virus, which is closely related to WN virus, is prevalent throughout East Asia. We evaluated the effectiveness of a focus reduction neutralization test in young chicks inoculated with JE and WN viruses, and conducted a survey of WN infection among wild birds in Far Eastern Russia. Following single virus infection, only neutralizing antibodies specific to the homologous virus were detected in chicks. The neutralization test was then applied to serum samples from 145 wild birds for WN and JE virus, Twenty-one samples were positive for neutralizing antibodies to WN. These results suggest that WN virus is prevalent among wild birds in the Far Eastern region of Russia.
  • Kentaro Yoshii, Keita Mottate, Yuki Omori-Urabe, Yumiko Chiba, Takahiro Seto, Takahiro Sanada, Junko Maeda, Mayumi Obara, Shuji Ando, Naoto Ito, Makoto Sugiyama, Hiroshi Sato, Hiroshi Fukushima, Hiroaki Kariwa, Ikuo Takashima  JOURNAL OF VETERINARY MEDICAL SCIENCE  73-  (3)  409  -412  2011/03  [Not refereed][Not invited]
     
    Tick-borne encephalitis virus (TBEV) is a zoonotic agent causing severe encephalitis in humans. Rodent species that are potential hosts for TBEV are widely distributed in various regions in Japan. In this study, we carried out large-scale epizootiological surveys in rodents from various areas of Japan. A total of 931 rodent and insectivore sera were collected from field surveys. Rodents seropositive for TBEV were found in Shimane Prefecture in Honshu and in several areas of Hokkaido Prefecture. These results emphasize the need for further epizootiological and epidemiological research of TBEV and preventive measures for emerging tick-borne encephalitis in Japan.
  • Ayae Ikawa-Yoshida, Kentaro Yoshii, Kazue Kuwahara, Mayumi Obara, Hiroaki Kariwa, Ikuo Takashima  MICROBIOLOGY AND IMMUNOLOGY  55-  (2)  100  -107  2011/02  [Not refereed][Not invited]
     
    Tick-borne encephalitis (TBE) virus causes severe encephalitis with serious sequelae in humans. An epizootiological survey of wild rodents is effective to detect TBE virus-endemic areas; however, limited serological diagnostic methods are available to detect anti-TBE virus antibodies in wild rodents. In this study, ELISAs for the detection of rodent antibodies against the TBE virus were developed using two recombinant proteins, domain III of the E protein (EdIII) and subviral particles (SPs), as the antigens. As compared with the neutralization test, the ELISA using EdIII had 77.1% sensitivity and 80.0% specificity, and the ELISA using SPs had 91.4% sensitivity and 100% specificity. Furthermore, when the ELISAs were applied to the epizootiological survey in the TBE virus-endemic area, both of the ELISAs was able to detect wild rodents with TBE virus-specific antibodies. This is the first study to show that ELISAs using recombinant antigens can be safe and useful in the detection of TBE virus-infected wild rodents in epizootiological research.
  • Kentaro Yoshii, Manabu Igarashi, Kimihito Ito, Hiroaki Kariwa, Michael R. Holbrook, Ikuo Takashima  VIRUS RESEARCH  155-  (1)  61  -68  2011/01  [Not refereed][Not invited]
     
    Omsk hemorrhagic fever virus (OHFV) is a member of the tick-borne encephalitis serocomplex of flaviviruses, and causes hemorrhagic disease in humans. In this study, an infectious cDNA of OHFV was constructed to investigate the molecular mechanisms involved in OHFV pathogenesis for the first time. Our cDNA clone was capable of producing infectious virus which is genetically identical to the parental Guriev strain, and the recombinant virus showed similar biological properties to the parental virus including growth kinetics and virulence characteristics. While characterizing the cDNAs, fortuitous mutations at NS2A position 46 and NS5 position 836 were found to affect viral production. By using a viral replicon expressing luciferase, it was shown that both of the mutations produced a defect in RNA replication and that the NS5 mutation induced a temperature-sensitive phenotype, indicating the importance of these residues in RNA replication. This infectious cDNA will be a useful tool to study the replication and pathogenesis of OHFV. (C) 2010 Elsevier B.V. All rights reserved.
  • Erdenesaikhan Tegshduuren, Kumiko Yoshimatsu, Midori Taruishi, Rika Endo, Kenta Shimizu, Takaaki Koma, Shumpei P. Yasuda, Hiroaki Kariwa, Jiro Arikawa, Chiaki Ishihara  COMPARATIVE IMMUNOLOGY MICROBIOLOGY AND INFECTIOUS DISEASES  33-  (6)  E67  -E73  2010/12  [Not refereed][Not invited]
     
    Tula virus (TULV) and Puumala virus (PUUV) are hantaviruses carried by the bank vole (Myodes glareolus) and European common vole (Microtus arvalis), respectively. PUUV is a causative agent of hemorrhagic fever with renal syndrome (HFRS), while TULV is thought to be apathogenic to humans. The N-terminal regions of the N proteins from TULV and PUUV were expressed and applied as enzyme-linked immunosorbent assay (ELISA) antigens. Colonized Japanese grass voles (Microtus montebelli) and BALB/c mice were used for experimental inoculation of the vole-borne hantaviruses TULV and PUUV. Voles and mice showed significant antibody production toward both viruses, but these antisera showed little cross-reactivity between TULV and PUUV in the immunofluorescence antibody assay and ELISA. In contrast, sera from patients with HFRS caused by PUUV exhibited high cross-reactivity against the TULV antigen, and sera from a natural rodent reservoir showed moderate cross-reactivity against the heterologous antigen, indicating that the antigenic cross-reactivity between TULV and PUUV differs in sera from rodents and humans. (C) 2010 Elsevier Ltd. All rights reserved.
  • Hyun-Kyoung Lee, Byoung-Hee Lee, Seung-Hyeok Seok, Min-Won Baek, Hui-Young Lee, Dong-Jae Kim, Yi-Rang Na, Kyoung-Jin Noh, Sung-Hoon Park, Dutta Noton Kumar, Hiroaki Kariwa, Mina Nakauchi, Suk-Jin Heo, Jae-Hak Park  JOURNAL OF VETERINARY SCIENCE  11-  (2)  165  -167  2010/06  [Not refereed][Not invited]
     
    Severe acute respiratory syndrome (SARS) is a life-threatening disease for which accurate diagnosis is essential. Although many tools have been developed for the diagnosis of SARS, false-positive reactions in negative sera may occur because of cross-reactivity with other coronaviruses. We have raised polyclonal and monoclonal antibodies (Abs) using a recombinant form of the SARS virus nucleocapsid protein. Cross-reactivity of these anti-SARS Abs against human coronavirus (HCoV) 229E and HCoV OC43 were determined by Western blotting. The Abs produced reacted with recombinant SARS virus nucleocapsid protein, but not with HCoV 229E or HCoV OC43.
  • Ryo Murata, Yuki Eshita, Akihiko Maeda, Junko Maeda, Saki Akita, Tomohisa Tanaka, Kentaro Yoshii, Hiroaki Kariwa, Takashi Umemura, Ikuo Takashima  AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE  82-  (4)  696  -704  2010/04  [Not refereed][Not invited]
     
    Many West Nile (WN) virus isolates associated with significant outbreaks possess a glycosylation site on the envelope (E) protein. E-protein glycosylated variants of New York (NY) strains of WN virus are more neuroinvasive in mice than the non-glycosylated variants. To determine how E protein glycosylation affects the interactions between WN virus and avian hosts, we inoculated young chicks with NY strains of WN virus containing either glycosylated or nonglycosylated variants of the E protein. The glycosylated variants were more virulent and had higher viremic levels than the non-glycosylated variants. The glycosylation status of the variant did not affect viral multiplication and dissemination in mosquitoes in vivo. Glycosylated variants showed more heat-stable propagation than non-glycosylated variants in mammalian (BHK) and avian (QT6) cells but not in mosquito (C6/36) cells. Thus, E-protein glycosylation may be a requirement for efficient transmission of WN virus from avian hosts to mosquito vectors.
  • Hiroaki Kariwa, Evgeniy A. Tkachenko, Vyacheslav G. Morozov, Takahiro Seto, Yoichi Tanikawa, Sergey I. Kolominov, Sergey N. Belov, Ichiro Nakamura, Nobuo Hashimoto, Alexander E. Balakiev, Tamara K. Dzagurnova, Nur Hardy bin Abu Daud, Daisuke Miyashita, Olga A. Medvedkina, Mina Nakauchi, Mariko Ishizuka, Kentaro Yoshii, Kumiko Yoshimatsu, Jiro Arikawa, Ikuo Takashima  JOURNAL OF VETERINARY MEDICAL SCIENCE  71-  (12)  1569  -1578  2009/12  [Not refereed][Not invited]
     
    European Russia is a highly endemic area of hemorrhagic fever with renal syndrome (HFRS), a rodent-borne zoonotic disease, caused by hantaviruses. In total, 145 small mammals of four species (Myodes glareolus, Apodemus flavicollis, A. agrarius, and A. uralensis) were trapped in the Samara region of European Russia in August 2005 and examined for the presence of hantavirus (HV). Anti-HV antibodies were found in six of 68 (8.8%) M. glareolus and in one of 19 (5.3%) A. flavicollis by indirect immunofluorescent antibody assay (IFA). The Puumala virus (PUUV), which is one of the hantavirus species, was detected in the lungs of seven M. glareolus by RT-PCR. The virus S-segment was extremely similar (96.2% to 99.3%) to the sequence found in a fatal case of HFRS in the Samara region. Phylogenetic analyses of S and M segments showed that the Samara PUUVs form a cluster within the Russian Volga lineage and apparently differ from other European PUUVs. Anti-PUUV antibodies were found in blood sera from seven HFRS patients and from one undiagnosed patient from the Samara region, using IFA and an enzyme-linked immunosorbent assay (ELISA). These data Suggest that the bank vole M. glareolus is a primary natural reservoir and vector for PUUV, which is the main causative agent of HFRS in humans in the Samara region.
  • Kentaro Yoshii, Ayae Ikawa, Yumiko Chiba, Yuki Omori, Junko Maeda, Ryo Murata, Hiroaki Kariwa, Ikuo Takashima  JOURNAL OF VIROLOGICAL METHODS  161-  (1)  173  -176  2009/10  [Not refereed][Not invited]
     
    Previously, a system for packaging tick-borne encephalitis virus (TBEV) subgenomic replicon RNAs into single-round infectious virus-like particles (VLPs) was developed. In the present study, VLPs were applied to measuring the levels of neutralizing antibodies against TBEV as an alternative to performing neutralization tests with live virus. As markers of VLP infection, the genes for GFP and luciferase were inserted into the TBEV replicon, which was then packaged into VLPs. The reporter genes were expressed in cells that were infected with the VLPs, and this infection was inhibited by neutralizing antibodies to TBEV. Serum samples from wild rodents were used to evaluate the neutralization test using VLPs. All the sera that were positive in the conventional neutralization test were also found to be positive in the neutralization test using VLPs, and there were highly significant correlations between the neutralization titres obtained using the native virus and those using VLPs. These results indicate that VLPs that express reporter genes represent a useful and safe alternative to conventional neutralization testing using live virus. (C) 2009 Elsevier B.V. All rights reserved.
  • Akihiko Maeda, Ryo Murata, Minoru Akiyama, Ikuo Takashima, Hiroaki Kariwa, Tomomasa Watanabe, Ichiro Kurane, Junko Maeda  VIRUS RESEARCH  144-  (1-2)  35  -43  2009/09  [Not refereed][Not invited]
     
    Viral reverse genetics, particularly infectious cloning, is a valuable tool with applications to many areas of viral research including the generation of vaccine candidates. However, this technology is sometimes insufficient for the construction cDNA clones as the genome sequences and/or encoding proteins of some viral agents may be toxic to the host cells used for cloning. To circumvent this problem, we developed a polymerase chain reaction (PCR)-based protocol for generating a complete West Nile virus (WNV) cDNA. The fragmented cDNAs were synthesized from WNV RNA by reverse transcription-PCR, and subsequently cloned into plasmids for use as templates for WNV cDNA synthesis. The fragmented cDNAs were amplified and assembled by PCR to generate a full-length WNV cDNA. Using this ONA as a template, WNV RNA was synthesized in vitro and transfected into mammalian cells. We also examined the generation of a mutant recombinant WNV containing a site-directed mutation within the viral genome sequence. Here, we discuss the possibility of developing a method for the generation of recombinant WNVs. (C) 2009 Elsevier B.V. All rights reserved.
  • Japanese Journal of Veterinary Research  57-  89  -99  2009  [Not refereed][Not invited]
  • Mina Nakauchi, Hiroaki Kariwa, Yasuhiro Kon, Kentaro Yoshii, Akihiko Maeda, Ikuo Takashima  MICROBIOLOGY AND IMMUNOLOGY  52-  (12)  625  -630  2008/12  [Not refereed][Not invited]
     
    SARS-CoV has four major structural proteins: the N, S, M, and E proteins. To investigate the mechanism of SARS-CoV assembly, we cloned the genes encoding these four proteins into the eukaryotic expression vector pCAGGS and transfected them into 293T cells. When all four expression vectors were co-transfected VLP formed, as confirmed using electron microscopy. Using a rabbit polyclonal antibody specific to the N protein, N-protein-containing particles similar in size to the VLP were also observed by immunoelectron microscopy, indicating that the VLP contained the N protein. Co-immunoprecipitation analyses demonstrated an interaction between the N and M proteins, suggesting that N protein binds directly to M protein to be incorporated into VLP.
  • Nur Hardy Abu Daud, Hiroaki Kariwa, Evgeniy Tkachenko, Tamara Dzagurnova, Olga Medvedkina, Petr Tkachenko, Mariko Ishizuka, Takahiro Seto, Daisuke Miyashita, Takahiro Sanada, Mina Nakauchi, Kentaro Yoshii, Akihiko Maeda, Kumiko Yoshimatsu, Jiro Arikawa, Ikuo Takashima  JAPANESE JOURNAL OF VETERINARY RESEARCH  56-  (3)  151  -165  2008/11  [Not refereed][Not invited]
     
    Puumala virus (PUUV), a causative agent of hemorrhagic fever with renal syndrome (HFRS), is prevalent in Europe and European Russia. No vaccine has been developed for PUUV-associated HFRS, primarily because of the low viral yield in cultured cells. A PUUV strain known as DTK/Ufa-97 was isolated in Russia and adapted for growth in Vero E6 cells maintained in serum-free medium. The DTK/Ufa-97 strain produced a higher viral titer in serum-free medium, suggesting that it may prove useful in the development of an HFRS vaccine. When PUUV-infected Vero E6 cells were grown in serum-free medium, the DTK/Ufa-97 strain yielded more copies of intracellular viral RNA and a higher viral titer in the culture fluid than did the Sotkamo strain. Phylogenetic analysis revealed that PUUVs can be classified into multiple lineages according to geographical origin, and that the DTK/Ufa-97 strain is a member of the Bashkiria-Saratov lineage. The deduced amino acid sequences of the small, medium, and large segments of the DTK/Ufa-97 strain were 99.2% to 100%, 99.3% to 99.8%, and 99.8% identical, respectively, to those of the Bashkirian PUUV strains and 96.9%, 92.6%, and 97.4% identical, respectively, to those of the Sotkamo strain, indicating that the PUUVs are genetically diverse. However, DTK/Ufa-97 and other strains of PUUV exhibited similar patterns of binding to a panel of monoclonal antibodies against Hantaan virus. In addition, diluted antisera (i.e., ranging from 1:160 to 1:640) specific to three strains of PUUV neutralized both homologous and heterologous viruses. These results suggest that the DTK/Ufa-97 strain is capable of extensive growth and is antigenically similar to genetically distant strains of PUUV.
  • Detection of Antibodies Against SARS-Coronavirus Using Recombinant Truncated Nucleocapsid Proteins by ELISA
    Hyun-Kyoung Lee, Byoung-Hee Lee, Noton Kumar Dutta, Seung-Hyeok Seok, Min-Won Baek, Hui-Young Lee, Dong-Jae Kim, Yi-Rang Na, Kyoung-Jin Noh, Sung-Hoon Park, Hiroaki Kariwa, Mina Nakauchi, Le Quynh Mai, Suk-Jin Heo, Jae-Hak Park  JOURNAL OF MICROBIOLOGY AND BIOTECHNOLOGY  18-  (10)  1717  -1721  2008/10  [Not refereed][Not invited]
     
    Severe acute respiratory syndrome (SARS) is a life-threatening emerging respiratory disease caused by the coronavirus, SARS-CoV The nucleocapsid (N) protein of SARS-CoV is highly antigenic and may be a suitable candidate for diagnostic applications. We constructed truncated recombinant N proteins (N1 |1-422 aa|, N2 |-109 aa|, and N3 |110-422 aa|) and determined their antigenicity by Western blotting using convalescent SARS serum. The recombinants containing N1 and N3 reacted with convalescent SARS serum in Western blotting. However, the recombinant with N2 did not. In ELISA using N1 or N3 as the antigens. positive results were observed in 10 of 10 (100%,) SARS-CoV-positive human sera. None of 50 healthy sera gave positive results in either assay. These data indicate that the ELISA using NI or N3 has high sensitivity and specificity. These results suggest that the middle or C-terminal region of the SARS N protein is important for eliciting antibodies against SARS-CoV during, the immune response, and ELISA reactions using N1 or N3 may be a valuable tool for SARS diagnosis.
  • Ichiro Nakamura, Kumiko Yoshimatsu, Byoung-Hee Lee, Megumi Okumura, Midori Taruishi, Koichi Araki, Hiroaki Kariwa, Ikuo Takashima, Jiro Arikawa  ARCHIVES OF VIROLOGY  153-  (8)  1537  -1542  2008/08  [Not refereed][Not invited]
     
    To distinguish Thailand virus infection from infections with other hantaviruses, we established an ELISA serotyping system using a truncated nucleocapsid protein of Thailand virus lacking 49 amino acids at the N-terminus. In evaluations using patient and rodent sera, Thailand virus infection was readily distinguished from Hantaan and Seoul virus infections. Therefore, this ELISA system is an effective alternative to neutralization tests.
  • Noton Kumar Dutta, Kaushiki Mazumdar, Byoung-Hee Lee, Min-Won Baek, Dong-Jae Kim, Yi-Rang Na, Sung-Hoon Park, Hyun-Kyoung Lee, Hiroaki Kariwa, Le Quynh Mai, Jae-Hak Park  IMMUNOLOGY LETTERS  118-  (1)  65  -71  2008/06  [Not refereed][Not invited]
     
    It is believed today that nucleocapsid protein (N) of severe acute respiratory syndrome (SARS)-CoV is one of the most promising antigen candidates for vaccine design. In this study, three fragments [NI (residues: 1-422); N2 (residues: 1-109); N3 (residues: 110-422)] of N protein of SARS-CoV were expressed in Escherichia coli and analyzed by pooled sera of convalescence phase of SARS patients. Three gene fragments [N1 (1-1269 nt), N2 (1-327 nt) and N3 (328-1269 nt)-expressing the same proteins of NI, N2 and N3, respectively] of SARS-N were cloned into pVAX-1 and used to immunize BALB/c mice by electroporation. Humoral (by enzyme-linked immunosorbent assay, ELISA) and cellular (by cell proliferation and CD4(+):CD8(+) assay) immunity was detected by using recombinant N1 and N3 specific antigen. Results showed that NI and N3 fragments of N protein expressed by E. coli were able to react with sera of SARS patients but N2 could not. Specific humoral and cellular immunity in mice could be induced significantly by inoculating SARS-CoV N1 and N3 DNA vaccine. In addition, the immune response levels in N3 were significantly higher for antibody responses (IgG and IgG1 but not IgG2a) and cell proliferation but not in CD4(+):CD8(+) assay compared to N1 vaccine. The identification of antigenic N protein fragments has implications to provide basic information for the design of DNA vaccine against SARS-CoV. The present results not only suggest that DNA immunization with pVax-N3 could be used as potential DNA vaccination approaches to induce antibody in BALB/c mice, but also illustrates that gene immunization with these SARS DNA vaccines can generate different immune responses. (c) 2008 Elsevier B.V. All rights reserved.
  • Hiroaki Kariwa, Hiroshi Noda, Mina Nakauchi, Mariko Ishizuka, Kazuaki Hashiguchi, Shingo Hashimoto, Kentaro Yoshii, Atsushi Asano, Takashi Agui, Hiroyuki Kogaki, Yoshihiro Kurano, Yoshiaki Uchida, Nobuyuki Fuji, Masahisa Okada, Ikuo Takashima  JAPANESE JOURNAL OF VETERINARY RESEARCH  55-  (4)  115  -127  2008/02  [Not refereed][Not invited]
     
    The sudden emergence of severe acute respiratory syndrome (SARS) at the end of 2002 resulted in 774 reported deaths from more than 8000 cases worldwide. As no effective vaccines or antiviral agents are available, the most effective measure to prevent the expansion of a SARS epidemic is the rapid diagnosis and isolation of SARS patients. To establish specific diagnostic methods, we generated nine clones of monoclonal antibodies to nucleocapsid protein (NP) of SARS-coronavirus (SARS-CoV). On immunofluorescent antibody assay and Western blotting analysis, none of the monoclonal antibodies showed cross-reactivity to authentic and recombinant NPs of human coronavirus (HCoV) 229E strain. To determine the region on the NP molecule where the monoclonal antibodies bind, we generated four truncated recombinant NPs and analyzed the reactivity between monoclonal antibodies and truncated NPs. Two monoclonal antibodies reacted with a truncated NP covering from amino acid residues 111 to 230, and seven reacted with another truncated NP covering from amino acid residues 221 to 340. Epitope mapping analysis indicated that monoclonal antibody SN5-25 recognized the amino acid sequence Q(245)TVTKW(250) on SARS-NP. Within the epitope, Q245, T246, V247, K249, and K250 appeared to form an essential motif for monoclonal antibody SN5-25 to bind. The information about binding sites and epitopes of monoclonal antibodies may be useful for the development of new diagnostic methods for SARS and for analyzing the function of N protein of SARS-CoV.
  • Kentaro Yoshii, Akiko Goto, Kazue Kawakami, Hiroaki Kariwa, Ikuo Takashima  JOURNAL OF GENERAL VIROLOGY  89-  (1)  200  -211  2008/01  [Not refereed][Not invited]
     
    We have previously reported a system for packaging tick-borne encephalitis (TBE) virus subgenomic replicon RNAs into single-round infectious virus-like particles (VLPs) by using in trans expression of viral C/prM/E structural proteins. In this study, the trans-packaging system was applied to the generation of chimeric VLPs with mosquito-borne Japanese encephalitis (JE) virus. Although trans-expression of TBE virus C and JE virus prM/E proteins resulted in the secretion of VLPs, the expression of JE virus C/prM/E proteins did not lead to the secretion of VLPs, suggesting that homologous interaction between C and non-structural proteins or the genomic RNA is important for efficient assembly of infectious particles. Neutralization testing showed that the antigenic characteristics of the VLPs; were similar to those of the native virus. Furthermore, the infectivities of the TBE virus- and JE virus-enveloped VLPs for the ISE6 tick cell line and C6/36 mosquito cell line were investigated. The VLPs were able to enter only those cells that were derived from the natural vectors for the respective viruses. TBE virus replicon RNA packaged in VLPs produced TBE virus non-structural proteins in tick cells, but could neither replicate nor produce viral proteins in mosquito cells. These findings indicate the importance of specific cellular factors for virus entry and replication during flavivirus infection of arthropods. These results demonstrate that chimeric VLPs are useful tools for the study of viral genome packaging and cellular factors involved in vector specificity, with the additional safety aspect that these chimeric VLPs can be used instead of full-length chimeric viruses.
  • Microbiology and Immunology  51-  (11)  1081  -1090  2007  [Not refereed][Not invited]
  • Kazuya Shirato, Hirotsugu Miyoshi, Hiroaki Kariwa, Ikuo Takashima  VIRUS RESEARCH  121-  (1)  11  -16  2006/10  [Not refereed][Not invited]
     
    The envelope (E) protein glycosylation status of the New York strain of West Nile (WN) virus is an important determinant of virus neuroinvasiveness. To elucidate the determinant of the difference between E protein-glycosylated and non-glycosylated WN virus infections, the cytokine expression of murine peritoneal macrophages infected with each virus was examined. Tumor necrosis factor (TNF) alpha and interleukin (IL)-1 beta were up-regulated with replication of the E protein-glycosylated virus. Interferon (IFN) beta and IL-6 were up-regulated with the clearance of both viruses. These results suggest that TNF alpha and IL-1 beta expression are related to the virulence of E protein-glycosylated WN virus. (c) 2006 Elsevier B.V. All rights reserved.
  • M Obara, K Yoshii, T Kawata, D Hayasaka, A Goto, T Mizutani, H Kariwa, Takashima, I  JOURNAL OF VIROLOGICAL METHODS  134-  (1-2)  55  -60  2006/06  [Not refereed][Not invited]
     
    The similarity of symptoms produced by tick-borne encephalitis (TBE) and Japanese encephalitis (JE) and the high degree of cross-reactivity between TBE and JE viruses by serological tests make the development of a differential diagnostic test a priority. In this study, recombinant prM/E proteins of TBE virus strain Oshima 5-10 expressed in mammalian cells resulted in the release of subviral particles (SPs) into the culture medium. Using the SPs as antigens, enzyme-linked immunosorbent assay (ELISA) systems were developed to detect TBE virus-specific IgM and IgG antibodies, designated SP-IgG and SP-IgM ELISAs, respectively. Of 83 serum samples from encephalitis patients in Khabarovsk, Russia, which were positive with the neutralization test (NT), 82 were positive by the SP-IgG ELISA, for a sensitivity of 98.8%, which was higher than that of a commercial ELISA kit. All 12 NT-negative samples were also negative by the SP-IgG ELISA (specificity, 100%). Of 17 patient samples that were NT-positive, 16 (94.1%) were positive by the SP-IgM ELISA. Of 15 paired serum samples that yielded equivocal results by NT, 11 had positive results with the SP-IgM ELISA, indicating a diagnosis of TBE infection. The SP-IgG and SP-IgM ELISAs showed no cross-reactivity with antibodies to the JE virus. The results indicate that these ELISAs will be useful for the detection of TBE-specific antibodies. (c) 2005 Elsevier B.V. All rights reserved.
  • T Okabayashi, H Kariwa, S Yokota, S Iki, T Indoh, N Yokosawa, Takashima, I, H Tsutsumi, N Fujii  JOURNAL OF MEDICAL VIROLOGY  78-  (4)  417  -424  2006/04  [Not refereed][Not invited]
     
    The pathogenesis of severe acute respiratory syndrome (SARS) is poorly understood and cytokine dysregulation has been suggested as one relevant mechanism to be explored. We compared the cytokine profile in Caco2 cells after infection of SARS coronavirus (SARS-CoV) with other respiratory viruses including respiratory syncytial virus (RSV), influenza A virus (FluAV), and human parainfluenza virus type 2 (hPIV2). Interferon (IFN) system (production and response) was not suppressed by SARS-CoV infection. Therefore, SARS-CoV replication was suppressed by pretreatment with IFN. SARS-CoV and RSV induced high levels of IL-6 and RANTES compared with FluAV and hPIV2. Induction level of suppressor of cytokine signaling-3 (SOCS3) by SARS-CoV was significantly lower than that by RSV in spite of the significant production of IL-6. Toll-like receptors 4 and 9, which correlate with the induction of inflammatory response, were upregulated by SARS-CoV infection. Collectively, overinduction of inflammatory cytokine and dysregulation of cytokine signaling may contribute to the immunopathology associated with "severe" inflammation in SARS.
  • LJ Baek, H Kariwa, K Lokugamage, K Yoshimatsu, J Arikawa, Takashima, I, JI Kang, SS Moon, SY Chung, EJ Kim, HJ Kang, KJ Song, TA Klein, R Yanagihara, JW Song  JOURNAL OF MEDICAL VIROLOGY  78-  (2)  290  -297  2006/02  [Not refereed][Not invited]
     
    Hantaan (HTN) virus, the etiologic agent of clinically severe hemorrhagic fever with renal syndrome (HFRS), was first isolated in 1976 from lung tissue of a striped-field mouse (Apodemus agrarius) captured in Songnae-ri, Gyeonggi Province, Republic of Korea. Found primarily in mountainous areas, the Korean field mouse (A. peninsulae) is the second-most dominant field rodent species found throughout Korea. A new hantavirus, designated Soochong (SOO), was isolated in Vero E6 cells from four A. peninsulae captured in August 1997 at Mt. Gyebang in Hongcheon-gun, Mt. Gachil, Inje-gun, Gangwon Province, and in September 1998 at Mt. Deogyu, Muju-gun, Jeollabuk Province. The entire S, M, and L genomic segments of SOO virus, amplified by RT-PCR from lung tissues of seropositive A. peninsulae and from virus-infected Vero E6 cells, diverged from HTN virus (strain 76-118) by 15.6%, 22.8%, and 21.7% at the nucleotide level and 3.5%, 9.5%, and 4.6% at the amino acid level, respectively. Phylogenetic analyses of the nucleotide and deduced amino acid sequences, using the maximum parsimony and neighbor-joining methods, indicated that SOO virus was distinct from A. agrarius-borne HTN virus. SOO virus shared a common ancestry with Amur virus from Far East Russia, as well as with H5 and B78 hantaviruses, previously isolated from HFRS patients in China. Cross-focus-reduction neutralizating antibody tests showed that SOO virus which is the first hantavirus isolated in cell culture from A. peninsulae, could be classified as a new hantavirus serotype.
  • Geographical distribution of hantaviruses in Thailand and potential human
    American Journal of Tropical Medicine and Hygiene  75-  (5)  994  -1002  2006  [Not refereed][Not invited]
  • H Kariwa, N Fujii, K Takashima  DERMATOLOGY  212-  (Suppl 1)  119  -123  2006  [Not refereed][Not invited]
     
    The efficacy of several povidone-iodine (PVP-I) products, a number of other chemical agents and various physical conditions were evaluated for their ability to inactivate the severe acute respiratory syndrome coronavirus; (SARS-CoV). Treatment of SARS-CoV with PVP-I products for 2 min reduced the virus infectivity from 1.17 x 10(6) TCID50/ml to below the detectable level. The efficacy of 70% ethanol was equivalent to that of PVP-I products. Fixation of SARS-CoV-infected Vero E6 cells with a fixative including formalin, glutaraldehyde, methanol and acetone for 5 min or longer eliminated all infectivity. Heating the virus at 56 degrees C for 60 min or longer reduced the infectivity of the virus from 2.6 x 10(7) to undetectable levels. Irradiation with ultraviolet light at 134 mu W/cm(2) for 15 min reduced the infectivity from 3.8 x 10(7) to 180 TCID50/ml; however, prolonged irradiation (60 min) failed to eliminate the remaining virus, leaving 18.8 TCID50/ml. Copyright (c) 2006 S. Karger AG, Basel.
  • Kogaki, H., Uchida, Y., Fujii, N., Kurano, Y., Miyake, K., Kido, Y., Kariwa, H., Takashima, I., Tamashiro, H., Ling, A.E., and Okada, M.:"Novel rapid immunochromatographic test based on an enzyme immunoassay for detecting nucleocapsid antigen in SARS-a・・・
    2005  [Not refereed][Not invited]
     
    Kogaki, H., Uchida, Y., Fujii, N., Kurano, Y., Miyake, K., Kido, Y., Kariwa, H., Takashima, I., Tamashiro, H., Ling, A.E., and Okada, M.:"Novel rapid immunochromatographic test based on an enzyme immunoassay for detecting nucleocapsid antigen in SARS-associated coronavirus", J Clin Lab Anal, 19:150-159. (2005)*
  • Yoshii, K., Hayasaka, D., Goto, A., Kawakami, K., Kariwa, H., and Takashima, I.:"Packaging the replicon RNA of the Far-Eastern subtype of tick-borne encephalitis virus into single-round infectious particles: development of a heterologous gene delivery ・・・
    2005  [Not refereed][Not invited]
     
    Yoshii, K., Hayasaka, D., Goto, A., Kawakami, K., Kariwa, H., and Takashima, I.:"Packaging the replicon RNA of the Far-Eastern subtype of tick-borne
    encephalitis virus into single-round infectious particles: development of a
    heterologous gene delivery system", Vaccine, 23:3946-3956.(2005)*
  • Shirato, K., Miyoshi, H., Kariwa, H., and Takashima, I.:"Detection of West Nile virus and Japanese encephalitis virus using real-time PCR with a probe common to both viruses", J Virol Methods, 126:119-125(2005)*
    2005  [Not refereed][Not invited]
  • Goto, A., Yoshii, K., Obara, M., Ueki, T., Mizutani, T., Kariwa, H., and Takashima, I.:"Role of the N-linked glycans of the prM and E envelope proteins in tick-borne encephalitis virus particle secretion", Vaccine, 23:3043-3052(2005)*
    2005  [Not refereed][Not invited]
  • Zamoto A, Tsuji M, Wei Q, Cho SH, Shin EH, Kim TS, Leonova GN, Hagiwara K, Asakawa M, Kariwa H, Takashima I, Ishihara C. Epizootiologic survey for Babesia microti among small wild mammals in northeastern Eurasia and a geographic diversity in the beta-t・・・
    2004  [Not refereed][Not invited]
     
    Zamoto A, Tsuji M, Wei Q, Cho SH, Shin EH, Kim TS, Leonova GN, Hagiwara K, Asakawa M, Kariwa H, Takashima I, Ishihara C. Epizootiologic survey for Babesia microti among small wild mammals in northeastern Eurasia and a geographic diversity in the beta-tubulin gene sequences. J Vet Med Sci. 66(7):785-792, 2004*
  • Shirato K, Miyoshi H, Goto A, Ako Y, Ueki T, Kariwa H, Takashima I. Viral envelope protein glycosylation is a molecular determinant of the neuroinvasiveness of the New York strain of West Nile virus. J Gen Virol. 85(Pt 12): 3637-3645, 2004.*
    2004  [Not refereed][Not invited]
  • Lokugamage K, Kariwa H, Lokugamage N, Iwasa M, Hagiya T, Araki K, Tachi A, Mizutani T, Yoshimatsu K, Arikawa J, Iwasaki T, Takashima I. Comparison of virulence of various hantaviruses related to hemorrhagic fever with renal syndrome in newborn mouse mo・・・
    2004  [Not refereed][Not invited]
     
    Lokugamage K, Kariwa H, Lokugamage N, Iwasa M, Hagiya T, Araki K, Tachi A, Mizutani T, Yoshimatsu K, Arikawa J, Iwasaki T, Takashima I. Comparison of virulence of various hantaviruses related to hemorrhagic fever with renal syndrome in newborn mouse model. Jpn J Vet Res. 51(3-4): 143-149, 2004.*
  • Araki K, Yoshimatsu K, Lee BH, Okumura M, Kariwa H, Takashima I, Arikawa J. Age-dependent hantavirus-specific CD8(+) T-cell responses in mice infected with Hantaan virus. Arch Virol. 149(7): 1373-1382, 2004.*
    2004  [Not refereed][Not invited]
  • Lokugamage N, Kariwa H, Lokugamage K, Iwasa MA, Hagiya T, Yoshii K, Tachi A, Ando S, Fukushima H, Tsuchiya K, Iwasaki T, Araki K, Yoshimatsu K, Arikawa J, Mizutani T, Osawa K, Sato H, Takashima I. Epizootiological and epidemiological study of hantavir・・・
    2004  [Not refereed][Not invited]
     
    Lokugamage N, Kariwa H, Lokugamage K, Iwasa MA, Hagiya T, Yoshii K, Tachi A, Ando S, Fukushima H, Tsuchiya K, Iwasaki T, Araki K, Yoshimatsu K, Arikawa J, Mizutani T, Osawa K, Sato H, Takashima I. Epizootiological and epidemiological study of hantavirus infection in Japan. Microbiol Immunol. 48(11): 843-851, 2004.*
  • Hayasaka D, Gritsun TS, Yoshii K, Ueki T, Goto A, Mizutani T, Kariwa H, Iwasaki T, Gould EA, Takashima I. Amino acid changes responsible for attenuation of virus neurovirulence in an infectious cDNA clone of the Oshima strain of tick-borne encephaliti・・・
    2004  [Not refereed][Not invited]
     
    Hayasaka D, Gritsun TS, Yoshii K, Ueki T, Goto A, Mizutani T, Kariwa H, Iwasaki T, Gould EA, Takashima I. Amino acid changes responsible for attenuation of virus neurovirulence in an infectious cDNA clone of the Oshima strain of tick-borne encephalitis virus. J Gen Virol. 85(Pt 4): 1007-1018, 2004.*
  • Iwasa MA, Kariwa H, Cui BZ, Lokugamage K, Lokugamage N, Hagiya T, Mizutani T, Takashima I. Modes of hantavirus transmission in a population of Clethrionomys rufocanus bedfordiae inferred from mitochondrial and microsatellite DNA analyses. Arch Virol.・・・
    2004  [Not refereed][Not invited]
     
    Iwasa MA, Kariwa H, Cui BZ, Lokugamage K, Lokugamage N, Hagiya T, Mizutani T, Takashima I. Modes of hantavirus transmission in a population of Clethrionomys rufocanus bedfordiae inferred from mitochondrial and microsatellite DNA analyses. Arch Virol. 149(5): 929-941, 2004.*
  • Lokugamage K, Kariwa H, Lokugamage N, Miyamoto H, Iwasa M, Hagiya T, Araki K, Tachi A, Mizutani T, Yoshimatsu K, Arikawa J, Takashima I. Genetic and antigenic characterization of the Amur virus associated with hemorrhagic fever with renal syndrome. Vir・・・
    2004  [Not refereed][Not invited]
     
    Lokugamage K, Kariwa H, Lokugamage N, Miyamoto H, Iwasa M, Hagiya T, Araki K, Tachi A, Mizutani T, Yoshimatsu K, Arikawa J, Takashima I. Genetic and antigenic characterization of the Amur virus associated with hemorrhagic fever with renal syndrome. Virus Res. 101(2): 127-134, 2004.*
  • Shirato K, Kimura T, Mizutani T, Kariwa H, Takashima I. Different chemokine expression in lethal and non-lethal murine West Nile virus infection. J Med Virol. 74(3): 507-513, 2004.*
    2004  [Not refereed][Not invited]
  • Kariwa H, Fujii N, Takashima I. Inactivation of SARS coronavirus by means of povidone-iodine, physical conditions, and chemical reagents. Jpn J Vet Res. 52(3): 105-112, 2004.*
    2004  [Not refereed][Not invited]
  • Yoshii K, Konno A, Goto A, Nio J, Obara M, Ueki T, Hayasaka D, Mizutani T, Kariwa H, Takashima I. Single point mutation in tick-borne encephalitis virus prM protein induces a reduction of virus particle secretion. J Gen Virol. 85(Pt 10):3049-3058, 20・・・
    2004  [Not refereed][Not invited]
     
    Yoshii K, Konno A, Goto A, Nio J, Obara M, Ueki T, Hayasaka D, Mizutani T, Kariwa H, Takashima I. Single point mutation in tick-borne encephalitis virus prM protein induces a reduction of virus particle secretion. J Gen Virol. 85(Pt 10):3049-3058, 2004.*
  • Mizutani, T., Kobayashi, M., Eshita, Y., Shirato, K., Kimura, T., Ako, Y., Miyoshi, H., Takasaki, T., Kurane, I., Kariwa, H., Umemura, T., and Takashima, I.:"Involvement of the JNK-like protein of the Aedes albopictus mosquito cell line, C6/36, in phag・・・
    2003  [Not refereed][Not invited]
     
    Mizutani, T., Kobayashi, M., Eshita, Y., Shirato, K., Kimura, T., Ako, Y., Miyoshi, H., Takasaki, T., Kurane, I., Kariwa, H., Umemura, T., and Takashima, I.:"Involvement of the JNK-like protein of the Aedes albopictus mosquito cell line, C6/36, in phagocytosis, endocytosis and infection of West Nile virus", Insect Molecular Biology, 12:491-499(2003)*
  • Goto, A., Hayasaka, D., Yoshii, K., Mizutani, T., Kariwa, H., and Takashima, I.:"A BHK-21 cell culture-adapted tick-borne encephalitis virus mutant is attenuated for neuroinvasiveness", Vaccine 21:4043-4051(2003)*
    2003  [Not refereed][Not invited]
  • Mizutani, T., Kobayashi, M., Eshita, Y., Inanami, O., Yamamori, T., Goto, A., Ako, Y., Miyoshi, H., Miyamoto, H., Kariwa, H., Kuwabara, M., and Takashima, I.:"Characterization of JNK-like protein derived from a mosquito cell line, C6/36", Insect Molec・・・
    2003  [Not refereed][Not invited]
     
    Mizutani, T., Kobayashi, M., Eshita, Y., Inanami, O., Yamamori, T., Goto, A., Ako, Y., Miyoshi, H., Miyamoto, H., Kariwa, H., Kuwabara, M., and Takashima, I.:"Characterization of JNK-like protein derived from a mosquito cell line, C6/36", Insect Molecular Biology, 12(1):61-66(2003)*
  • Kariwa, H., Tanabe, H., Mizutani, T., Kon, Y., Lokugamage, K., Lokugamage, N., Iwasa, M.A., Hagiya, T., Araki, K., Yoshimatsu, K., Arikawa, J., and Takashima, I.:"Synthesis of Seoul virus RNA and structural proteins in cultured cells", Archives of Viro・・・
    2003  [Not refereed][Not invited]
     
    Kariwa, H., Tanabe, H., Mizutani, T., Kon, Y., Lokugamage, K., Lokugamage, N., Iwasa, M.A., Hagiya, T., Araki, K., Yoshimatsu, K., Arikawa, J., and Takashima, I.:"Synthesis of Seoul virus RNA and structural proteins in cultured cells", Archives of Virology 148:1671-1685(2003)*
  • Lee, B.H., Yoshimatsu, K., Araki, K., Ogino, M., Okumura, M., Tsuchiya, K., Kariwa, H., and Arikawa, J.:"Detection of antibody for the serodiagnosis of hantavirus infection in different rodent species", Archives of Virology, 148:1885-1897(2003)*
    2003  [Not refereed][Not invited]
  • Shirato, K., Mizutani, T., Kariwa, H., and Takashima, I.:"Discrimination of West Nile virus and Japanese encephalitis virus strains using RT-PCR RFLP analysis", Microbiology and Immunology, 47:439-445(2003)*
    2003  [Not refereed][Not invited]
  • Miyamoto, H., Kariwa, H., Araki, K., Lokugamage, K., Hayasaka, D., Cui, B.Z., Lokugamage, N., Ivanov, L.I., Mizutani, T., Iwasa, M.A., Yoshimatsu, K., Arikawa, J., and Takashima, I.:" Serological analysis of hemorrhagic fever with renal syndrome (HFRS)・・・
    2003  [Not refereed][Not invited]
     
    Miyamoto, H., Kariwa, H., Araki, K., Lokugamage, K., Hayasaka, D., Cui, B.Z., Lokugamage, N., Ivanov, L.I., Mizutani, T., Iwasa, M.A., Yoshimatsu, K., Arikawa, J., and Takashima, I.:" Serological analysis of hemorrhagic fever with renal syndrome (HFRS) patients in Far Eastern Russia and identification of the causative hantavirus genotype", Archives of Virology, 148:1543-1556(2003)*
  • Araki, K., Yoshimatsu, K., Lee, B.H., Kariwa, H., Takashima, I., and Arikawa, J.:"Hantavirus-specific CD8(+)-T-cell responses in newborn mice persistently infected with Hantaan virus", Journal of Virology, 77:8408-8417(2003)*
    2003  [Not refereed][Not invited]
  • Lokugamage, N., Kariwa, H., Lokugamage, K., Hagiya, T., Miyamoto, H., Iwasa, M.A., Araki, K., Yoshimatsu, K., Arikawa, J., Mizutani, T., and Takashima, I.:"Development of an efficient method for recovery of Puumala and Puumala-related viruses by inocul・・・
    2003  [Not refereed][Not invited]
     
    Lokugamage, N., Kariwa, H., Lokugamage, K., Hagiya, T., Miyamoto, H., Iwasa, M.A., Araki, K., Yoshimatsu, K., Arikawa, J., Mizutani, T., and Takashima, I.:"Development of an efficient method for recovery of Puumala and Puumala-related viruses by inoculation of Mongolian gerbils", Journal of Veterinary Medical Science 65:1189-1194(2003)*
  • Yoshii, K., Hayasaka, D., Goto, A., Obara, M., Araki, K., Yoshimatsu, K., Arikawa, J., Ivanov, L., Mizutani, T., Kariwa, H., and Takashima, I.:"Enzyme-linked immunosorbent assay using recombinant antigens expressed in mammalian cells for serodiagnosis ・・・
    2003  [Not refereed][Not invited]
     
    Yoshii, K., Hayasaka, D., Goto, A., Obara, M., Araki, K., Yoshimatsu, K., Arikawa, J., Ivanov, L., Mizutani, T., Kariwa, H., and Takashima, I.:"Enzyme-linked immunosorbent assay using recombinant antigens expressed in mammalian cells for serodiagnosis of tick-borne encephalitis", Journal of Virological Methods, 108:171-179(2003)*
  • Goto, A., Hayasaka, D., Yoshii, K., Mizutani, T., Kariwa, H., Takashima, I. :"Genetic and biological comparison of tick-borne encephalitis viruses from Hokkaido and far-eastern Russia": Jpn J Vet Res, 49:297-307(2002)*
    2002  [Not refereed][Not invited]
  • Lokugamage, K., Kariwa, H., Hayasaka, D., Cui, B.Z., Iwasaki, T., Lokugamage, N., Ivanov, L.I., Volkov, V.I., Demenev, V.A., Slonova, R., Kompanets, G., Kushnaryova, T., Kurata, T., Maeda, K., Araki, K., Mizutani, T., Yoshimatsu, K., Arikawa, J., Takas・・・
    2002  [Not refereed][Not invited]
     
    Lokugamage, K., Kariwa, H., Hayasaka, D., Cui, B.Z., Iwasaki, T., Lokugamage, N., Ivanov, L.I., Volkov, V.I., Demenev, V.A., Slonova, R., Kompanets, G., Kushnaryova, T., Kurata, T., Maeda, K., Araki, K., Mizutani, T., Yoshimatsu, K., Arikawa, J., Takashima, I.:"Genetic characterization of hantaviruses transmitted by the Korean field mouse (Apodemus peninsulae), Far East Russia"
    Emerg Infect Dis, 8:768-776(2002)*
  • Yahara, Y., Ohkubo, Y., Kariwa, H., Takashima, I.:"Evaluation of enzyme-linked immunosorbent assay (ELISA) and immunofluorescent antibody (IFA) test for the detection of porcine reproductive and respiratory syndrome virus (PRRSV) antibody in pigs from ・・・
    2002  [Not refereed][Not invited]
     
    Yahara, Y., Ohkubo, Y., Kariwa, H., Takashima, I.:"Evaluation of enzyme-linked immunosorbent assay (ELISA) and immunofluorescent antibody (IFA) test for the detection of porcine reproductive and respiratory syndrome virus (PRRSV) antibody in pigs from conventional farms"
    J Vet Med Sci, 64:583-588(2002)*
  • Wang, H., Yoshimatsu, K., Ebihara, H., Ogino, M., Araki, K., Kariwa, H., Wang, Z., Luo, Z., Li, D., Hang, C. and Arikawa, J.: "Genetic diversity of hantaviruses isolated in china and characterization of novel hantaviruses isolated from Niviventer confu・・・
    2000  [Not refereed][Not invited]
     
    Wang, H., Yoshimatsu, K., Ebihara, H., Ogino, M., Araki, K., Kariwa, H., Wang, Z., Luo, Z., Li, D., Hang, C. and Arikawa, J.: "Genetic diversity of hantaviruses isolated in china and characterization of novel hantaviruses isolated from Niviventer confucianus and Rattus rattus", Virology, 278:332-345(2000)*
  • Kariwa, H., Yoshimatsu, K., Araki, K., Chayama, K., Kumada, H., Ogino, M., Ebihara, H., Murphy, M.E., Mizutani, T., Takashima, I. and Arikawa, J.: "Detection of hantaviral antibodies among patients with hepatitis of unknown etiology in Japan", Microbio・・・
    2000  [Not refereed][Not invited]
     
    Kariwa, H., Yoshimatsu, K., Araki, K., Chayama, K., Kumada, H., Ogino, M., Ebihara, H., Murphy, M.E., Mizutani, T., Takashima, I. and Arikawa, J.:
    "Detection of hantaviral antibodies among patients with hepatitis of unknown etiology in Japan", Microbiology and Immunology, 44:357-362(2000)*
  • Ebihara, H., Yoshimatsu, K., Ogino, M., Araki, K., Ami, Y., Kariwa, H., Takashima I, Li, D. and Arikawa J.: "Pathogenicity of Hantaan virus in newborn mice: genetic reassortant study demonstrating that a single amino acid change in glycoprotein G1 is・・・
    2000  [Not refereed][Not invited]
     
    Ebihara, H., Yoshimatsu, K., Ogino, M., Araki, K., Ami, Y., Kariwa, H., Takashima I, Li, D. and Arikawa J.: "Pathogenicity of Hantaan virus in newborn mice: genetic reassortant study demonstrating that a single amino acid change in glycoprotein G1
    is related to virulence", Journal of Virology, 74:9245-9255(2000)*
  • Murphy, M.E., Kariwa, H., Mizutani, T., Yoshimatsu, K., Arikawa, J. and Takashima I.: "In vitro antiviral activity of lactoferrin and ribavirin upon hantavirus", Archives of Virology, 145:1571-1582(2000)*
    2000  [Not refereed][Not invited]
  • 2000  [Not refereed][Not invited]
     
    Mizutani, T., Inagaki, H., Tada, M., Hayasaka, D., Murphy, M., Fujiwara, T., Hamada, J., Kariwa, H. and Takashima, I.: "The mechanism of actinomycin D-mediated increase of Borna disease virus (BDV) RNA in cells persistently infected by BDV", Microbiology and Immunology, 44:597-603(2000)*
  • Komoro, K., Hayasaka, D., Mizutani, T., Kariwa, H. and Takashima, I.: "Characterization of monoclonal antibodies against Hokkaido strain tick-borne encephalitis virus", Microbiology and Immunology,44:533-536(2000)*
    2000  [Not refereed][Not invited]
  • Kariwa H, Yoshimatsu K, Sawabe J, Yokota E, Arikawa J, Takashima I, Fukushima H, Lundkvist A, Shubin FN, Isachkova LM, Slonova RA, Leonova GN, Hashimoto N.:"Genetic diversities of hantaviruses among rodents in Hokkaido, Japan and Far East Russia", Viru・・・
    1999  [Not refereed][Not invited]
     
    Kariwa H, Yoshimatsu K, Sawabe J, Yokota E, Arikawa J, Takashima I, Fukushima H, Lundkvist A, Shubin FN, Isachkova LM, Slonova RA, Leonova GN, Hashimoto N.:"Genetic diversities of hantaviruses among rodents in Hokkaido, Japan and Far East Russia", Virus Res., 59(2):219-28 (1999)*
  • Hayasaka D, Suzuki Y, Kariwa H, Ivanov L, Volkov V, Demenev V, Mizutani T, Gojobori T, Takashima I.:"Phylogenetic and virulence analysis of tick-borne encephalitis viruses from Japan and far-Eastern Russia", J Gen Virol., 80 (12):3127-3135 (1999)*
    1999  [Not refereed][Not invited]
  • Mizutani T, Inagaki H, Hayasaka D, Kariwa H, Takashima I.:"Enhancement of Borna disease virus transcription in persistently infected cells by serum starvation", J Vet Med Sci., 61(7):831-834 (1999)*
    1999  [Not refereed][Not invited]
  • Chiba N, Osada M, Komoro K, Mizutani T, Kariwa H, Takashima I.:"Protection against tick-borne encephalitis virus isolated in Japan by active and passive immunization", Vaccine., 17(11-12):1532-1539 (1999)*
    1999  [Not refereed][Not invited]
  • Mizutani T, Nishino Y, Kariwa H, Takashima I.:"Reverse transcription-nested polymerase chain reaction for detecting p40 RNA of Borna disease virus, without risk of plasmid contamination", J Vet Med Sci., 61(1):77-80 (1999)*
    1999  [Not refereed][Not invited]
  • Mizutani T, Ogino M, Nishino Y, Kimura T, Inagaki H, Hayasaka D, Kariwa H, Takashima I.:"Single-step reverse transcriptase-polymerase chain reaction for detection of Borna disease virus RNA in vitro and in vivo", Jpn J Vet Res., 46(4):165-169 (1999)*
    1999  [Not refereed][Not invited]
  • Tsujimura K, Mizutani T, Kariwa H, Yoshimatsu K, Ogino M, Morii Y, Inagaki H, Arikawa J, Takashima I.:"A serosurvey of Borna disease virus infection in wild rats by a capture ELISA", J Vet Med Sci., 61(2):113-7 (1999)*
    1999  [Not refereed][Not invited]
  • Chiba N, Iwasaki T, Mizutani T, Kariwa H, Kurata T, Takashima I.:"Pathogenicity of tick-borne encephalitis virus isolated in Hokkaido, Japan in mouse model", Vaccine., 17(7-8):779-787 (1999)*
    1999  [Not refereed][Not invited]
  • *Kariwa, H., Fujiki, M., Yoshimatsu, K., Arikawa, J., Takashima, I., Hashimoto, N. "Urine-associated horizontal transmission of Seoul virus among rats", Archives of Virology, 143: 15-24 (1998)*
    1998  [Not refereed][Not invited]
  • Morii, M., Yoshimatsu, K., Arikawa, J., Zhou, G, Kariwa, H., Takashima, I. "Antigenic characterization of Hantaan and Seoul virus nucleocapsid proteins expressed by recombinant baculovirus: application of a truncated protein, lacking an antigenic regio・・・
    1998  [Not refereed][Not invited]
     
    Morii, M., Yoshimatsu, K., Arikawa, J., Zhou, G, Kariwa, H., Takashima, I. "Antigenic characterization of Hantaan and Seoul virus nucleocapsid proteins expressed by recombinant baculovirus: application of a truncated protein, lacking an antigenic region common to the two viruses, as a serotyping antigen", Journal of Clinical Microbiology, 36: 2514-2521 (1998) *
  • Takashima, I., Morita, K., Chiba, M., Hayasaka, D., Sato, T., Takezawa, C., Igarashi, A., Kariwa, H., Yoshimatsu, K., Arikawa, J. and Hashimoto, N. : "A case of tick-borne encephalitis in Japan and isolation of the the virus", J. Clin. Microbiol., 35 :・・・
    1997  [Not refereed][Not invited]
     
    Takashima, I., Morita, K., Chiba, M., Hayasaka, D., Sato, T., Takezawa, C., Igarashi, A., Kariwa, H., Yoshimatsu, K., Arikawa, J. and Hashimoto, N. : "A case of tick-borne encephalitis in Japan and isolation of the the virus", J. Clin. Microbiol., 35 : 1943-1947 (1997)*
  • Ennis, F. A., Cruz, J., Spiropoulou, C. F., Waite, D., Peters, C. J., Nichol, S. T., Kariwa, H. and Koster, F. T. : "Hantavirus pulmonary syndrome : CD8+ and CD4+ cytotoxic T lymphocytes to epitopes on Sin Nombre virus nucleocapsid protein isolated dur・・・
    1997  [Not refereed][Not invited]
     
    Ennis, F. A., Cruz, J., Spiropoulou, C. F., Waite, D., Peters, C. J., Nichol, S. T., Kariwa, H. and Koster, F. T. : "Hantavirus pulmonary syndrome : CD8+ and CD4+ cytotoxic T lymphocytes to epitopes on Sin Nombre virus nucleocapsid protein isolated during acute illness", Virology, 238 : 380-390 (1997)*
  • K. Yoshimatsu, J. Arikawa, H. Li, H. Kariwa and N. Hashimoto : "Western blotting using recombinant Hantaan virus nucleocapsid protein expressed in silkworm as a serological confirmation of hantavirus infection in human sera", J. Vet. Med. Sci., 58 : 71・・・
    1996  [Not refereed][Not invited]
     
    K. Yoshimatsu, J. Arikawa, H. Li, H. Kariwa and N. Hashimoto : "Western blotting using recombinant Hantaan virus nucleocapsid protein expressed in silkworm as a serological confirmation of hantavirus infection in human sera", J. Vet. Med. Sci., 58 : 71-74 (1996)*
  • A. Ito, M. Okamoto, H. Kariwa, T. Ishiguro, A. Hashimoto and M. Nakao : "Antibody responses against Echinococcus multilocularis antigens in naturally infected Rattus norvegicus", J. Helminthol., 70 : 355-357 (1996)*
    1996  [Not refereed][Not invited]
  • I. Takashima, M. Hiyoshi, H. Kariwa, R. Mukaiya and N. Hashimoto : "Experimental Chlamydia psittaci infection of Japanese quail", Microbiol. Immunol., 40 : 265-701 (1996)*
    1996  [Not refereed][Not invited]
  • I. Takashima, Y. Imai, N. Itoh, H. Kariwa and N. Hashimoto : "Polymerase chain reaction for the detection of Chlamydia psittaci in the feces of budgerigars", Microb. Immunol., 40 : 21-26 (1996)*
    1996  [Not refereed][Not invited]
  • H. Kariwa, M. Kimura, S. Yoshizumi, J. Arikawa, K. Yoshimatsu, I. Takashima and N. Hashimoto : "Different modes of Seoul virus infection : persistency in newborn rats and transiency in adult rats", Arch. Virol., 141 : 2327-2338 (1996)*
    1996  [Not refereed][Not invited]

Awards & Honors

  • 2007/04 The Japanese Society of Veterinary Science The Award of the Japanese Society of Veterinary Science
     Comparative epidemiological study of hantavirus infection among wild rodents 
    受賞者: KARIWA Hiroaki

Research Grants & Projects

  • 野生鳥獣類に由来するウイルス性人獣共通感染症の診断法開発と比較疫学的研究
    日本学術振興会:科学研究費補助金
    Date (from‐to) : 2013/04 -2017/03 
    Author : 苅和 宏明
  • 近隣地域からの侵入が危惧されるわが国にない感染症の発生予防に関する研究
    厚生労働省:厚生労働科学研究費補助金
    Date (from‐to) : 2013/04 -2016/03 
    Author : 苅和 宏明
  • 海外からの侵入が危惧される野生鳥獣媒介性感染症の疫学、診断・予防法等に関する研究
    厚生労働省:厚生労働科学研究費補助金
    Date (from‐to) : 2010/04 -2013/03 
    Author : 苅和 宏明
  • わが国とアメリカ大陸のウイルス性人獣共通感染症の流行阻止のための研究
    日本学術振興会:科学研究費補助金
    Date (from‐to) : 2009/04 -2013/03 
    Author : 苅和 宏明
  • 国内で発生のないベクター媒介性感染症の疫学診断法等の研究
    厚生労働省:厚生労働科学研究費補助金
    Date (from‐to) : 2007/04 -2010/03 
    Author : 苅和 宏明
  • 日本に侵入する危険性の高い北米産ウイルス性人獣共通感染症の疫学的研究
    日本学術振興会:科学研究費補助金
    Date (from‐to) : 2004/04 -2008/03 
    Author : 苅和 宏明
  • 日本と極東ロシアの野生げっ歯類を病原巣動物とする人獣共通感染症の比較疫学的研究
    日本学術振興会:科学研究費補助金
    Date (from‐to) : 2001/04 -2004/03 
    Author : 苅和 宏明
  • わが国のげっ歯類を病原巣動物とするウイルス性人獣共通感染症の疫学的研究
    日本学術振興会:科学研究費補助金
    Date (from‐to) : 2001/04 -2004/03 
    Author : 苅和 宏明
  • SARSコロナウイルスのウイルス粒子形成機構に関する研究
    Date (from‐to) : 2003
  • Study on the mechanism of virion formation of SARS-coronavirus
    Date (from‐to) : 2003
  • 本邦と極東ロシアのげっ歯類におけるハンタウイルスの比較疫学的研究
    日本学術振興会:科学研究費補助金
    Date (from‐to) : 1998/04 -2000/03 
    Author : 苅和 宏明
  • フラビウイルスの疫学的研究
    Date (from‐to) : 1999
  • Epidemiological study of flaviviruses
    Date (from‐to) : 1999
  • わが国の野性げっ歯類におけるハンタウイルスの感染調査と新型ハンタウイルスの分離
    日本学術振興会:科学研究費補助金
    Date (from‐to) : 1995/04 -1996/03 
    Author : 苅和 宏明
  • ハンタウイルスの生態学的研究
    Date (from‐to) : 1990
  • Ecological study of hantaviruses
    Date (from‐to) : 1990

Educational Activities

Teaching Experience

  • 感染症学特別研究Ⅰ
    開講年度 : 2018
    課程区分 : 博士後期課程
    開講学部 : 国際感染症学院
  • Environmental Hygiene
    開講年度 : 2018
    課程区分 : 学士課程
    開講学部 : 獣医学部
    キーワード : 環境破壊、環境汚染、化学汚染物質、生体防御、規制
  • 感染症学特別演習
    開講年度 : 2018
    課程区分 : 博士後期課程
    開講学部 : 国際感染症学院
  • Zoonotic Science
    開講年度 : 2018
    課程区分 : 学士課程
    開講学部 : 獣医学部
    キーワード : 人獣共通感染症、新興・再興感染症、疫学、自然宿主、媒介動物、感染環、ウイルス、細菌、原虫、寄生虫 
  • 人獣共通感染症対策専門特論
    開講年度 : 2018
    課程区分 : 博士後期課程
    開講学部 : 国際感染症学院
  • Milk and Meat Hygiene
    開講年度 : 2018
    課程区分 : 学士課程
    開講学部 : 農学部
    キーワード : 畜産食品、乳、肉、食品衛生、食中毒
  • 感染症学特別研究ⅡA
    開講年度 : 2018
    課程区分 : 博士後期課程
    開講学部 : 国際感染症学院
  • Veterinary Public Health
    開講年度 : 2018
    課程区分 : 学士課程
    開講学部 : 獣医学部
    キーワード : 獣医衛生, 国民衛生の動向, 獣医疫学, 感染症・非感染症の疫学, 感染症の予防と防疫, 環境衛生と環境汚染
  • 感染症学特別研究ⅡB
    開講年度 : 2018
    課程区分 : 博士後期課程
    開講学部 : 国際感染症学院
  • Practice in Veterinary Public Health
    開講年度 : 2018
    課程区分 : 学士課程
    開講学部 : 獣医学部
    キーワード : 環境衛生と環境汚染, 大気の衛生, 上水・下水・汚水, 水質検査、感染症、人獣共通感染症
  • 海外インターンシップA
    開講年度 : 2018
    課程区分 : 博士後期課程
    開講学部 : 国際感染症学院
  • 海外インターンシップB
    開講年度 : 2018
    課程区分 : 博士後期課程
    開講学部 : 国際感染症学院
  • 獣医科学・感染症学基礎科目 獣医公衆衛生学特論
    開講年度 : 2018
    課程区分 : 博士後期課程
    開講学部 : 国際感染症学院
  • 獣医科学特別研究
    開講年度 : 2018
    課程区分 : 博士後期課程
    開講学部 : 獣医学研究科
  • 人獣共通感染症対策専門特論
    開講年度 : 2018
    課程区分 : 博士後期課程
    開講学部 : 獣医学研究科
  • 獣医科学特論演習
    開講年度 : 2018
    課程区分 : 博士後期課程
    開講学部 : 獣医学研究科
  • 獣医科学基礎科目B 獣医公衆衛生学特論
    開講年度 : 2018
    課程区分 : 博士後期課程
    開講学部 : 獣医学研究科
  • インターンシップ
    開講年度 : 2018
    課程区分 : 博士後期課程
    開講学部 : 獣医学院
  • 獣医科学基礎科目 獣医公衆衛生学特論
    開講年度 : 2018
    課程区分 : 博士後期課程
    開講学部 : 獣医学院
  • 獣医公衆衛生学演習
    開講年度 : 2018
    課程区分 : 学士課程
    開講学部 : 獣医学部
  • 研究・臨床セミナー
    開講年度 : 2018
    課程区分 : 学士課程
    開講学部 : 獣医学部
  • アドバンスト演習
    開講年度 : 2018
    課程区分 : 学士課程
    開講学部 : 獣医学部


Copyright © MEDIA FUSION Co.,Ltd. All rights reserved.