Researcher Database

Isoda Norikazu
Research Center for Zoonosis Control
Specially Appointed Associate Professor

Researcher Profile and Settings


  • Research Center for Zoonosis Control

Job Title

  • Specially Appointed Associate Professor

Research funding number

  • 80615732

J-Global ID

Research Activities

Published Papers

  • Osamu Noyori, Keita Matsuno, Masahiro Kajihara, Eri Nakayama, Manabu Igarashi, Makoto Kuroda, Norikazu Isoda, Reiko Yoshida, Ayato Takada
    VIROLOGY 446 (1-2) 152 - 161 0042-6822 2013/11 [Refereed][Not invited]
    The viral envelope glycoprotein (GP) is thought to play important roles in the pathogenesis of filovirus infection. It is known that GP expressed on the cell surface forms a steric shield over host proteins such as major histocompatibility complex class I and integrin pi, which may result in the disorder of cell-to-cell contacts and/or inhibition of the immune response. However, it is not clarified whether this phenomenon contributes to the pathogenicity of filoviruses. In this study, we found that the steric shielding efficiency differed among filovirus strains and was correlated with the difference in their relative pathogenicities. While the highly glycosylated mucin-like region of GP was indispensable, the differential shielding efficiency did not necessarily depend on the primary structure of the mucin-like region, suggesting the importance of the overall properties (e.g., flexibility and stability) of the GP molecule for efficient shielding of host proteins. (C) 2013 Elsevier Inc. All rights reserved.
  • Saya Kuribayashi, Yoshihiro Sakoda, Takeshi Kawasaki, Tomohisa Tanaka, Naoki Yamamoto, Masatoshi Okamatsu, Norikazu Isoda, Yoshimi Tsuda, Yuji Sunden, Takashi Umemura, Noriko Nakajima, Hideki Hasegawa, Hiroshi Kida
    PLOS ONE 8 (7) e68375  1932-6203 2013/07 [Refereed][Not invited]
    Highly pathogenic avian influenza viruses (HPAIVs) cause lethal infection in chickens. Severe cases of HPAIV infections have been also reported in mammals, including humans. In both mammals and birds, the relationship between host cytokine response to the infection with HPAIVs and lethal outcome has not been well understood. In the present study, the highly pathogenic avian influenza viruses A/turkey/Italy/4580/1999 (H7N1) (Ty/Italy) and A/chicken/Netherlands/2586/2003 (H7N7) (Ck/NL) and the low pathogenic avian influenza virus (LPAIV) A/chicken/Ibaraki/1/2005 (H5N2) (Ck/Ibaraki) were intranasally inoculated into chickens. Ty/Italy replicated more extensively than Ck/NL in systemic tissues of the chickens, especially in the brain, and induced excessive mRNA expression of inflammatory and antiviral cytokines (IFN-gamma, IL-1 beta, IL-6, and IFN-alpha) in proportion to its proliferation. Using in situ hybridization, IL-6 mRNA was detected mainly in microglial nodules in the brain of the chickens infected with Ty/Italy. Capillary leakage assessed by Evans blue staining was observed in multiple organs, especially in the brains of the chickens infected with Ty/Italy, and was not observed in those infected with Ck/NL. In contrast, LPAIV caused only local infection in the chickens, with neither apparent cytokine expression nor capillary leakage in any tissue of the chickens. The present results indicate that an excessive cytokine response is induced by rapid and extensive proliferation of HPAIV and causes fatal multiple organ failure in chickens.
  • Norikazu Isoda, Yoshimi Tsuda, Shingo Asakura, Masatoshi Okamatsu, Yoshihiro Sakoda, Hiroshi Kida
    ARCHIVES OF VIROLOGY 157 (12) 2257 - 2264 0304-8608 2012/12 [Refereed][Not invited]
    Avian influenza viruses A/duck/Mongolia/47/2001 (H7N1) (47/01) and A/duck/Mongolia/867/2002 (H7N1) (867/02) were defined as low-pathogenic avian influenza viruses (LPAIVs) using an intravenous pathogenicity test in chickens. On the other hand, the intracerebral pathogenicity indices of 47/01 and 867/02 were 1.30 and 0.00, respectively. A series of reassortant viruses were generated between 47/01 and 867/02, and their intracerebral pathogenicity was compared in one-day-old chicks to identify the protein(s) responsible for the intracerebral pathogenicity of 47/01. The results indicate that the amino acids at positions 50 and 98 of the nucleoprotein are related to the pathogenicity of 47/01 in chicks by intracerebral inoculation. A significant association was found between mortality of the chicks inoculated intracerebrally with 47/01 and virus replication in the lungs and/or brain. These results indicate that the NP of avian influenza viruses may be responsible for intracerebral pathogenicity in the host.
  • Yoshihiro Sakoda, Michiko Naito, Mutsumi Ito, Yuki Ito, Norikazu Isoda, Tomohisa Tanaka, Takashi Umemura, Hiroshi Kida
    JOURNAL OF VETERINARY MEDICAL SCIENCE 74 (7) 955 - 958 0916-7250 2012/07 [Refereed][Not invited]
    Leptospira interrogans serovar Manilae strain UP-MMC was inoculated into miniature pigs to assess its pathogenicity. Leptospires were recovered from the whole blood, kidneys, and livers in the acute phase without showing any clinical signs. Under immunosuppressive conditions by dexamethasone, leptospires were recovered from the kidneys and their genes were detected from the urine in the chronic phase. These results indicate that leptospires persisted in the kidneys until the chronic phase, and excretion of leptospires in the urine was enhanced under immunosuppressive conditions, resulting in horizontal transmission among pigs on farms.
  • Yoshihiro Sakoda, Masatoshi Okamatsu, Norikazu Isoda, Naoki Yamamoto, Koichi Ozaki, Yasuto Umeda, Shigeyuki Aoyama, Hiroshi Kida
    MICROBIOLOGY AND IMMUNOLOGY 56 (7) 490 - 495 0385-5600 2012/07 [Refereed][Not invited]
    Affinity chromatography using sulfated, spherical cellulose beads (Cellufine Sulfate) was assessed for purification of influenza A and influenza B viruses. Recovery rates of viruses eluted from the beads were high for all tested virus strains. This method was also useful for removing chicken egg-derived impurities from allantoic fluids containing influenza viruses; the hemagglutination activity per amount of protein in the eluted sample was significantly higher than that in the applied sample. These results suggest that use of Cellufine Sulfate is a practical method for primary purification of influenza viruses in the process of influenza vaccine production.
  • Norikazu Isoda, Yoshihiro Sakoda, Masatoshi Okamatsu, Yoshimi Tsuda, Hiroshi Kida
    ARCHIVES OF VIROLOGY 156 (4) 557 - 563 0304-8608 2011/04 [Refereed][Not invited]
    The avian influenza vaccine strain A/duck/Hokkaido/Vac-1/2004 (H5N1) (Vac-1) was found to be pathogenic in chicken embryos (CEs). In order to decrease the pathogenicity of Vac-1 in CEs, a series of reassortant viruses was generated between Vac-1 and A/Puerto Rico/8/1934 (H1N1) (PR8), and their pathogenicity and growth potential were compared in CEs. The results indicated that either the PB1 or PA protein was responsible for the pathogenicity of Vac-1 in CEs. The HA titers of the allantoic fluids of CEs inoculated with the recombinant H5N1 viruses, of which pathogenicity was lower than that of the recombinant Vac-1 prepared by reverse genetics in CEs, were equivalent to those of CEs inoculated with the recombinant Vac-1. One of the reassortant viruses, rg-PR8-PA/Vac-1 (H5N1), in which the PA gene was replaced with the corresponding gene of PR8, yielded allantoic fluids with the same HA titer as that of Vac-1, indicating that this reassortant should be a good candidate as an improved vaccine strain.
  • Natsumi Takeyama, Kenji Minari, Masahiro Kajihara, Norikazu Isoda, Ryuichi Sakamoto, Takashi Sasaki, Norihide Kokumai, Noriyasu Takikawa, Rikiya Shiraishi, Masaji Mase, Junko Hagiwara, Toshiaki Kodama, Takashi Imamura, Masashi Sakaguchi, Toshiaki Ohgitani, Akira Sawata, Masatoshi Okamatsu, Masatake Muramatsu, Kenji Tsukamoto, Zhifeng Lin, Kotaro Tuchiya, Yoshihiro Sakoda, Hiroshi Kida
    VETERINARY MICROBIOLOGY 147 (3-4) 283 - 291 0378-1135 2011/01 [Refereed][Not invited]
    H5 and H7 highly pathogenic avian influenza virus (HPAIV) represent a major global concern in poultries and human health. Avian influenza (AI) vaccines are available but not preferred for field applications, primarily because vaccination interferes with sero-surveillances of AIV infection. To overcome the problem, ELISA systems using nonstructural protein 1 (NS1) of AIV as antigens (NS1-ELISA) have been developed to measure anti-NS1 antibodies that are raised in AIV-infected but not in vaccinated chickens. However, some AI-vaccinated chickens having a weak anti-virus immune response may subsequently be infected with AIV and spread the virus. This raises a concern for the validity of NS1-ELISA to detect AIV infection in previously vaccinated chickens. In this study, we developed NS1-ELISA and assessed its feasibility to detect HPAIV infection in chickens previously immunized with H5 or H7 AI vaccines. The results indicated that the NS1-ELISA could identify HPAIV infection in both unvaccinated and vaccinated chickens at 1 week after infection in correlation with results from time-consuming virus isolation tests. Taken together, the NS1-ELISA system would be valuable tool to define HPAIV infection when AI vaccine program is in place. (C) 2010 Elsevier B.V. All rights reserved.
  • Masatoshi Okamatsu, Tomohisa Tanaka, Naoki Yamamoto, Yoshihiro Sakoda, Takashi Sasaki, Yoshimi Tsuda, Norikazu Isoda, Norihide Kokumai, Ayato Takada, Takashi Umemura, Hiroshi Kida
    VIRUS GENES 41 (3) 351 - 357 0920-8569 2010/12 [Refereed][Not invited]
    In April and May 2008, whooper swans (Cygnus cygnus) were found dead in Hokkaido in Japan. In this study, an adult whooper swan found dead beside Lake Saroma was pathologically examined and the identified H5N1 influenza virus isolates were genetically and antigenically analyzed. Pathological findings indicate that the swan died of severe congestive edema in the lungs. Phylogenetic analysis of the HA genes of the isolates revealed that they are the progeny viruses of isolates from poultry and wild birds in China, Russia, Korea, and Hong Kong. Antigenic analyses indicated that the viruses are distinguished from the H5N1 viruses isolated from wild birds and poultry before 2007. The chickens vaccinated with A/duck/Hokkaido/Vac-1/2004 (H5N1) survived for 14 days after challenge with A/whooper swan/Hokkaido/1/2008 (H5N1), although a small amount of the challenge virus was recovered from the tissues of the birds. These findings indicate that H5N1 highly pathogenic avian influenza viruses are circulating in wild birds in addition to domestic poultry in Asia and exhibit antigenic variation that may be due to vaccination.
  • Yoshihiro Sakoda, Sengee Sugar, Damdinjav Batchluun, Tseren-Ochir Erdene-Ochir, Masatoshi Okamatsu, Norikazu Isoda, Kosuke Soda, Hiroki Takakuwa, Yoshimi Tsuda, Naoki Yamamoto, Noriko Kishida, Keita Matsuno, Eri Nakayama, Masahiro Kajihara, Ayaka Yokoyama, Ayato Takada, Ruuragchaa Sodnomdarjaa, Hiroshi Kida
    VIROLOGY 406 (1) 88 - 94 0042-6822 2010/10 [Refereed][Not invited]
    H5N1 highly pathogenic avian influenza (HPAI) viruses were isolated from dead wild waterfowl at Khunt, Erkhel, Doityn Tsagaan, Doroo, and Ganga Lakes in Mongolia in July 2005, May 2006, May 2009, July 2009, and May 2010, respectively. The isolates in 2005 and 2006 were classified into genetic clade 2.2, and those in 2009 and 2010 into clade 2.3.2. A/whooper swan/Mongolia/6/2009 (H5N1) experimentally infected ducks and replicated systemically with higher mortality than that of the isolates in 2005 and 2006. Intensive surveillance of avian influenza in migratory waterfowl flying from their nesting lakes in Siberia to Mongolia in every autumn indicate that HPAI viruses have not perpetuated at their nesting lakes until 2009. The present results demonstrate that wild waterfowl were sporadically infected with H5N1 HPAI viruses prevailing in domestic poultry in the southern Asia and died in Mongolia on the way back to their northern territory in spring. (C) 2010 Elsevier Inc. All rights reserved.
  • Fei Feng, Nobuaki Miura, Norikazu Isoda, Yoshihiro Sakoda, Masatoshi Okamatsu, Hiroshi Kida, Shin-Ichiro Nishimura
    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS 20 (12) 3772 - 3776 0960-894X 2010/06 [Refereed][Not invited]
    We designed and synthesized novel trivalent anti-influenza reagents. Sialyllactose was located at the terminal of each valence which aimed to block each receptor-binding site of the hemagglutinin (HA) trimer on the surface of the virus. Structural analyses were carried out with a model which was constructed with a computer simulation. A previously reported cyclic glycopeptide blocker [Ohta, T.; Miura, N.; Fujitani, N.; Nakajima, F.; Niikura, K.; Sadamoto, R.; Guo, C.-T.; Suzuki, T.; Suzuki, Y.; Monde, K.; Nishimura, S.-I. Angew. Chem. Int. Ed., 2003, 42, 5186] bound to the HA in the model. The analyses suggest that the glutamine residue in the cyclic peptide bearing Neu5A alpha 2,3Gal beta 1,4Glc trisaccharide via a linker interacts with the Gln189 in HA through hydrogen bonding. The present anti-influenza reagents likely interact with a glutamine residue included in the vicinity of Gln189. A plague reduction assay of the influenza virus, A/PR/8/1934 (H1N1),was performed in MDCK cells to evaluate for the synthesized compounds to inhibit viral replication. One of the compounds showed approximately 85% inhibition at the concentration of 400 mu M at 4 degrees C. (C) 2010 Elsevier Ltd. All rights reserved.
  • Yasushi Itoh, Hiroichi Ozaki, Hirohito Ishigaki, Yoshihiro Sakoda, Tomoya Nagata, Kosuke Soda, Norikazu Isoda, Taichiro Miyake, Hideaki Ishida, Kiyoko Okamoto, Misako Nakayama, Hideaki Tsuchiya, Ryuzo Torii, Hiroshi Kida, Kazumasa Ogasawara
    VACCINE 28 (3) 780 - 789 0264-410X 2010/01 [Refereed][Not invited]
    Development of H7N7 highly pathogenic avian influenza virus (HPAIV) vaccines is an urgent issue since human cases of infection with this subtype virus have been reported and most humans have no immunity against H7N7 viruses. We made an H7N7 vaccine combining components from an influenza virus library of non-pathogenic type A influenza viruses Antibody and T cell recall responses specific against the vaccine strain were elicited by subcutaneous inoculation with the whole virus particle vaccine with or without alum as an adjuvant in cynomolgus macaques. No significant difference was observed in magnitude of antibody responses between vaccination with alum and vaccination without alum, though vaccination with alum induced longer recall responses of CD8(+) T cells than did vaccination without alum. After challenge with a subtype of H7N7 HPAIV, the virus was detected in nasal swabs of unvaccinated macaques for 8 days but only for I day in the animals vaccinated either with or without alum, although the macaques vaccinated with alum showed elevated body temperature more briefly after infection. These findings demonstrated that this H7N7 HPAIV strain is pathogenic to macaques and that the vaccine conferred protective immunity to macaques against H7N7 HPAIV infection. (C) 2009 Elsevier Ltd. All rights reserved.
  • Manuela Ocana-Macchi, Michael Bel, Laurence Guzylack-Piriou, Nicolas Ruggli, Matthias Liniger, Kenneth C. McCullough, Yoshihiro Sakoda, Norikazu Isoda, Mikhail Matrosovich, Artur Summerfield
    JOURNAL OF VIROLOGY 83 (24) 12947 - 12955 0022-538X 2009/12 [Refereed][Not invited]
    Although current H5N1 highly pathogenic avian influenza viruses (HPAIV) are inefficiently transmitted to humans, infected individuals can suffer from severe disease, often progressing rapidly to acute respiratory distress syndrome and multiorgan failure. This is in contrast with the situation with human influenza viruses, which in immunocompetent individuals usually cause only a respiratory disease which is less aggressive than that observed with avian H5N1 viruses. While the biological basis of inefficient transmission is well documented, the mechanisms by which the H5N1 viruses cause fatal disease remain unclear. In the present study, we demonstrate that human pulmonary microvascular endothelial cells (hPMEC) had a clearly higher susceptibility to infection by H5N1 HPAIV than to infection by human influenza viruses. This was measurable by de novo intracellular nucleoprotein production and virus replication. It was also related to a relatively higher binding capacity to cellular receptors. After infection of hPMEC, cell activation markers E-selectin and P-selectin were upregulated, and the proinflammatory cytokines interleukin-6 and beta interferon were secreted. H5N1 virus infection was also associated with an elevated rate of cell death. Reverse genetics analyses demonstrated a major role for the viral hemagglutinin in this cell tropism. Overall, avian H5N1 viruses have a particular receptor specificity targeting endothelial cells that is different from human influenza viruses, and this H5N1 receptor specificity could contribute to disease pathogenesis.
  • Kanako Moritoh, Hideto Yamauchi, Atsushi Asano, Kentaro Yoshii, Hiroaki Kariwa, Ikuo Takashima, Norikazu Isoda, Yoshihiro Sakoda, Hiroshi Kida, Nobuya Sasaki, Takashi Agui
    JAPANESE JOURNAL OF VETERINARY RESEARCH 57 (2) 89 - 99 0047-1917 2009/08 [Refereed][Not invited]
    Mx1 (Myxovirus resistance protein) and Oas1b (Oligoadenylate synthetase-1), induced by type 1 interferon (IFN), play a role in early antiviral innate immunity by inhibiting the replication of viruses. In mice, Mx1 and Oas1b confer resistance to the infection of orthomyxoviruses including influenza viruses and flaviviruses including West Nile viruses, respectively. Laboratory mice have been used to study the mechanisms of the pathogenesis of these virus infections; however, it is possible that they are not a suitable model system to study these viruses, since most of the inbred laboratory mouse strains lack both genes. It has been reported that feral mouse-derived inbred strains show resistance to the infection of these viruses due to the presence of intact both genes. In this study, we generated congenic strains in which the Mx or Oas locus of the MSM/Ms (MSAI) mouce was introduced to the most widely used mouse strain, C57BL/6J (136). B6.MSM-Mx mice showed resistance to the infection of influenza virus but not of West Nile virus. On the other hand, B6.MSM-Oas mice showed resistance to the infection of West Nile virus but not of influenza virus. Our results indicate that Mx1 and Oas1b show highly antiviral specificity in mice possessing the same genetic background. Therefore, these congenic mice are useful for not only infection study but also investigation of host defense mechanism to these viruses.
  • Yoshimi Tsuda, Norikazu Isoda, Yoshihiro Sakoda, Hiroshi Kida
    VIRUS RESEARCH 140 (1-2) 194 - 198 0168-1702 2009/03 [Refereed][Not invited]
    Many influenza A viruses form plaques on Madin-Darby canine kidney (MDCK) cells in the presence of trypsin. A/duck/Siberia/272/1998 (H13N6) (Sib272), however, does not form plaque on MDCK cells. After three blind passages of the strain on MDCK cells, plaque-forming variant was obtained and designated as A/duck/Siberia/272PF/1998 (H13N6) (Sib272PF). Genetic and functional analyses of Sib272 and Sib272PF revealed that amino acid substitutions, F3L of the HA2 subunit and T379K of the PB1, were responsible for plaque formation of Sib272PF by enhancing fusion and polymerase activities, respectively. (c) 2009 Elsevier B.V. All rights reserved.
  • Takashi Sasaki, Norikazu Isoda, Kosuke Soda, Ryuichi Sakamoto, Kazue Saijo, Junko Hagiwara, Norihide Kokumai, Toshiaki Ohgitani, Takashi Imamura, Akira Sawata, Zhifeng Lin, Yoshihiro Sakoda, Hiroshi Kida
    JAPANESE JOURNAL OF VETERINARY RESEARCH 56 (4) 189 - 198 0047-1917 2009/02 [Refereed][Not invited]
    Test vaccines comprised of inactivated water-in-oil emulsions containing various antigen levels were prepared using a non-pathogenic H5N1 avian influenza (AI) virus, A/duck/Hokkaido/Vac-1/04 (H5N1). The potencies of these test vaccines were evaluated by two experiments. In the first experiment, the triangular relationship among the antigen levels of test vaccines, the hemagglutination inhibition (HI) antibody response, and the protective effect against challenge with a highly pathogenic avian influenza (HPAI) virus, A/chicken/Yamaguchi/7/04 (H5N1), was confirmed. Then lasting immunity of chickens after a single-shot vaccination was confirmed in the second experiment. As a result, complete protection after the challenge was observed in chickens immunized by test vaccines with an antigen level of 160 HA units/dose or higher. Thus, it was ascertained that the minimum antigen level in the AI vaccine was 160 RA units/dose, and the minimum HI antibody titer that could protect chickens from HPAI virus infection-related death was considered to be 1:16. Dose-dependent III antibody responses were observed in chickens after the vaccination. Thus, 640 RA units/dose was thought to be similar to the optimal antigen level. Alternatively, the HI antibody titers of chickens, injected with the vaccine containing 640 HA units/dose, were maintained at 1:181 or higher for 100 weeks after the single-shot vaccination.
  • Masatoshi Okamatsu, Yoshihiro Sakoda, Noriko Kishida, Norikazu Isoda, Hiroshi Kida
    ARCHIVES OF VIROLOGY 153 (12) 2189 - 2195 0304-8608 2008/12 [Refereed][Not invited]
    The hemagglutinins (HAs) of H9 influenza viruses isolated from birds and mammals of different species were antigenically and genetically analyzed. Antigenic variants were selected from A/swine/Hong Kong/10/98 (H9N2) and A/duck/Hokkaido/13/00 (H9N2) in the presence of monoclonal antibodies (MAbs). Based on the reactivity patterns of these mutants with a panel of MAbs, at least five non-overlapping antigenic sites were defined using eight MAbs which recognized seven distinct epitopes on the H9 HA molecule. Based on the reactivity patterns with the panel of monoclonal antibodies, 21 H9N2 virus strains isolated from birds and mammals were divided into 7 antigenically distinct groups. The present findings indicate that it is important to monitor the antigenic variation in H9 influenza viruses. The panel of MAbs in the present study, thus, should be useful for detailed antigenic analysis of the H9 HAs for epidemiological studies, the selection of vaccine strains, and diagnosis.
  • Kosuke Soda, Hiroichi Ozaki, Yoshihiro Sakoda, Norikazu Isoda, Yoshinari Haraguchi, Saori Sakabe, Noritaka Kuboki, Noriko Kishida, Ayato Takada, Hiroshi Kida
    ARCHIVES OF VIROLOGY 153 (11) 2041 - 2048 0304-8608 2008/11 [Refereed][Not invited]
    In order to prepare H5N1 influenza virus vaccine, the hemagglutinins (HAs) of 14 H5 virus isolates from water birds in Asia were antigenically and genetically analyzed. Phylogenetic analysis of the H5 HA genes revealed that 13 isolates belong to Eurasian and the other one to North American lineages. Each of the deduced amino acid sequences of the HAs indicated a non-pathogenic profile. Antigenic analysis using a panel of monoclonal antibodies recognizing six different epitopes on the HA of A/duck/Pennsylvania/10218/1984 (H5N2) and chicken antiserum to an H5N1 reassortant strain generated between A/duck/Mongolia/54/2001 (H5N2) and A/duck/Mongolia/47/2001 (H7N1), [R(Dk/Mong-Dk/Mong) (H5N1)] showed that the HAs of highly pathogenic avian influenza (HPAI) viruses currently circulating in Asia were antigenically closely related to those of the present isolates from water birds. Mice subcutaneously injected with formalin-inactivated R(Dk/Mong-Dk/Mong) were protected from challenge with 100 mouse lethal dose of A/Viet Nam/1194/2004 (H5N1). The present results support the notion that the H5 isolates and the reassortant H5N1 strain should be useful for vaccine preparation.
  • Rashid Manzoor, Yoshihiro Sakoda, Aaron Mweene, Yoshimi Tsuda, Noriko Kishida, Gui-Rong Bai, Ken-Ichiro Kameyama, Norikazu Isoda, Kosuke Soda, Michiko Naito, Hiroshi Kida
    VIRUS GENES 37 (2) 144 - 152 0920-8569 2008/10 [Refereed][Not invited]
    During 2000-2007, 218 influenza viruses of 28 different combinations of HA (H1-H13) and NA (N1-N9) subtypes were isolated from fecal samples of free-flying water birds at two distant lakes in Hokkaido, Japan. Phylogenic analysis of the matrix (M) genes of 67 strains, selected on the basis of their subtype combinations, revealed that A/duck/Hokkaido/W95/2006 (H10N8) was a reassortant whose M gene belonged to North American non-gull-avian and the other seven genes to Eurasian non-gull-avian lineages. The M genes of other 65 strains belonged to Eurasian non-gull-avian and the one to Eurasian-gull lineages. The M genes of 65 strains were grouped into three different sublineages, indicating that influenza viruses circulating in different populations of free-flying water birds have evolved independently in nature.
  • Norikazu Isoda, Yoshihiro Sakoda, Noriko Kishida, Kosuke Soda, Saori Sakabe, Ryuichi Sakamoto, Takashi Imamura, Masashi Sakaguchi, Takashi Sasaki, Norihide Kokumai, Toshiaki Ohgitani, Kazue Saijo, Akira Sawata, Junko Hagiwara, Zhifeng Lin, Hiroshi Kida
    ARCHIVES OF VIROLOGY 153 (9) 1685 - 1692 0304-8608 2008/09 [Refereed][Not invited]
    A reassortant influenza virus, A/duck/Hokkaido/Vac-1/2004 (H5N1) (Dk/Vac-1/04), was generated between non-pathogenic avian influenza viruses isolated from migratory ducks in Asia. Dk/Vac-1/04 (H5N1) virus particles propagated in embryonated chicken eggs were inactivated with formalin and adjuvanted with mineral oil to form a water-in-oil emulsion. The resulting vaccine was injected intramuscularly into chickens. The chickens were challenged with either of the highly pathogenic avian influenza virus strains A/chicken/Yamaguchi/7/2004 (H5N1) or A/swan/Mongolia/3/2005 (H5N1) at 21 days post-vaccination (p. v.), when the geometric mean serum HI titers of the birds was 64 with the challenge virus strains. The vaccinated chickens were protected from manifestation of disease signs upon challenge with either of the highly pathogenic avian influenza viruses. However, challenge virus was recovered at low titers from the birds at 2 and 4 days post-challenge (p.c.). All 3 chickens challenged at 6 days p.v. died, whereas 3 chickens challenged at 8 days p.v. survived. These results indicate that the present vaccine confers clinical protection and reduction of virus shedding against highly pathogenic avian influenza virus challenge and should be useful as an optional tool in emergency cases.
  • Noriko Kishida, Yoshihiro Sakoda, Mai Shiromoto, Gui-Rong Bai, Norikazu Isoda, Ayato Takada, Graeme Laver, Hiroshi Kida
    VIRUS GENES 37 (1) 16 - 21 0920-8569 2008/08 [Refereed][Not invited]
    To investigate the prevalence of influenza viruses in feral water birds in the Southern Hemisphere, fecal samples of terns were collected on Heron Island, Australia, in December 2004. Six H2N5 influenza viruses were isolated. This is the first report of the isolation of the H2 subtype from shore birds in Australia. Phylogenetic analysis revealed that the M gene belonged to the American lineage of avian influenza viruses and the other genes belonged to the Eurasian lineages, indicating that genetic reassortment occurs between viruses of Eurasian and American lineages in free flying birds in nature.
  • Toshihiro Sawai, Yasushi Itoh, Hiroichi Ozaki, Norikazu Isoda, Kiyoko Okamoto, Yoshitaka Kashima, Yoshihiro Kawaoka, Yoshihiro Takeuchi, Hiroshi Kida, Kazumasa Ogasawara
    IMMUNOLOGY 124 (2) 155 - 165 0019-2805 2008/06 [Refereed][Not invited]
    We investigated whether a vaccine derived from an apathogenic reassortant type A H5N1 influenza strain could induce immune responses in vivo that mediated protection from highly pathogenic avian influenza virus infection in mice. After two subcutaneous immunizations with formalin-inactivated H5N1 whole virus particles (whole particle vaccine), significant killing specific for cells presenting a nucleoprotein peptide from the vaccine strain of the virus was observed. Similar vaccination with viruses treated with ether and formalin, which are commonly used for humans as ether-split vaccines, induced little or no cytotoxic T-cell response. Furthermore, whole particle vaccines of the apathogenic H5N1 strain were more effective than ether-split vaccines at inducing antibody production able to neutralize a highly pathogenic H5N1 strain. Finally, whole particle vaccines of H5N1 protected mice against infection by an H5N1 highly pathogenic avian influenza virus more effectively than did ether-split vaccines. These results suggest that formalin-inactivated virus particles of apathogenic strains are effective for induction of both cytotoxic T-lymphocyte and antibody responses against highly pathogenic avian influenza viruses in vivo, resulting in protection from infection by a highly pathogenic H5N1 virus.
  • Saori Sakabe, Yoshihiro Sakoda, Yoshinari Haraguchi, Norikazu Isoda, Kosuke Soda, Hiroki Takakuwa, Kazue Saijo, Akira Sawata, Katsumi Kume, Junko Hagiwara, Kotaro Tuchiya, Zhifeng Lin, Ryuichi Sakamoto, Takashi Imamura, Takashi Sasaki, Norihide Kokumai, Yoshihiro Kawaoka, Hiroshi Kida
    VACCINE 26 (17) 2127 - 2134 0264-410X 2008/04 [Refereed][Not invited]
    During 2001-2004, 41 H7 influenza viruses (2 H7N1 and 39 H7N7 strains) were isolated from fecal samples of migratory ducks that flew from Siberia in the autumn of each year to Japan and Mongolia. A phylogenetic analysis of the hemagglutinin (HA) genes of the nine representative isolates revealed that they belonged to the Eurasian Lineage and the deduced amino acid sequence at the cleavage site of the HAs represented apathogenic profiles. One of the H7 isolates A/duck/Mongolia/736/02 (H7N7) was chosen from these H7 isolates for the preparation of the test vaccine. To improve the growth potential of A/duck/Mongolia/ 736/02 (H7N7) in chicken embryos, A/duck/Hokkaido/Vac-2/04 (H7N7) was generated by genetic reassortment between A/duck/Mongolia/736/02 (H7N7) as the donor of the PB2, PB1, PA, HA, NA, and NS genes and A/duck/Hokkaido/49/98 (H9N2) as that of NP and M genes. The test vaccine was prepared as follows; A/duck/Hokkaido/Vac-2/04 (H7N7) was propagated in chicken embryos and the virus in the allantoic fluid was inactivated and adjuvanted to form an oil-in-water emulsion. The test vaccine conferred immunity to chickens, completely protecting the manifestation of clinical signs against the challenge with lethal dose of H7 highly pathogenic avian influenza virus. These results indicate that influenza viruses isolated from natural reservoirs are useful for vaccine strains. (C) 2008 Elsevier Ltd. All rights reserved.
  • Development of vaccine strains of H5 and H7 influenza viruses
    Kosuke Soda, Yoshihiro Sakoda, Norikazu Isoda, Masahiro Kajihara, Yoshinari Haraguchi, Hitomi Shibuya, Hiromi Yoshida, Takashi Sasaki, Ryuichi Sakamoto, Kazue Saijo, Junko Hagiwara, Hiroshi Kida
    JAPANESE JOURNAL OF VETERINARY RESEARCH 55 (2-3) 93 - 98 0047-1917 2008/01 [Refereed][Not invited]
    To establish vaccine strains of H5 and H7 influenza viruses, A/duck/Hokkaido/Vac-1/04 (H5N1) [Vac-1/04 (H5N1)], A/duck/Hokkaido/Vac-3/07 (H5N1) [Vac-3/07 (H5N1)], and A/duck/Hokkaido/ Vac-2/04 (H7N7) [Vac-2/04 (H7N7)] were generated from non-pathogenic avian influenza viruses isolated from migratory ducks. Vac-1/04 (H5N1) and Vac-3/07 (H5N1) were generated by genetic reassortment between H5N2 or H5N3 virus as an HA gene provider and H7N1 or H6N1 viruses as an NA gene provider. Vac-2/04 (H7N7) was a genetic reassortant obtained using H7N7 and H9 N2 viruses to give high growth character of the H9N2 virus in chicken embryonated eggs. The results of sequence analyses and experimental infections revealed that these H5N1 and H7N7 reassortant viruses were non-pathogenic in chickens and embryos, and had good growth potential in embryonated eggs. These viruses should be useful to develop vaccines against H5 and H7 highly pathogenic avian influenza viruses.

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
  • 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
  • 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
  • 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
  • 国際感染症学コア科目Ⅰ 人獣共通感染症制御学特論
    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
  • 国際感染症学コア科目ⅡA リスク分析学特論
    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
  • 国際感染症学コア科目ⅡA 国際保健衛生演習
    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
  • 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
  • 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 獣医リスク解析学特論
    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
  • 獣医科学基礎科目B 国際保健衛生特論
    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

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