①デルタレトロウイルスによる白血病発症機構の解明

　成人T細胞白血病の原因ウイルスに最も近縁な牛白血病ウイルスを対象として、Taxタンパク質と白血病潜伏期間の関係を調べ、白血病発症におけるTaxタンパク質の役割を明らかにする。得られる成果は、成人T細胞白血病の早期診断や発症予防・治療法の開発につながることが期待される。

1. Kanno T., Ishihara R., Mori H., Tomiyasu T., Okazaki K., Impact of amino acid 233 in Tax on bovine leukemia virus infection in Japanese Black cattle., Res Vet Sci, 154, 102-107 (2023)
2. Tomiyasu T., Mori H., Okazaki K., Epidemiological evidence for early-onset of enzootic bovine leukosis by L233-Tax-carrying bovine leukemia virus in Japanese Black cattle, J Vet Med Sci, 84, 1216–1220 (2022)
3. Lo CW., Borjigin L., Saito S, Fukunaga K, Saitou E., Okazaki K., Mizutani T., Wada S., Takeshima S., Aida Y., BoLA-DRB3 Polymorphism is Associated with Differential Susceptibility to Bovine Leukemia Virus-Induced Lymphoma and Proviral Load., Viruses, 12(3), 352-352 (2020)
4. Tomiyasu Y., SatoA., Mori H., Okazaki Y., L233P mutation in the bovine leukemia virus Tax protein has impact on annexin A3 and type I collagen secretion by host cells., Vet Microbiol, 256, 109042-109042 (2021)
5. Mori H., Tomiyasu T., Nishiyama K., Matsumoto M., Osawa Y., Okazaki K., L233P mutation in the bovine leukemia virus Tax protein depresses endothelial cell recruitment and tumorigenesis in athymic nude mice., Arch Virol, 164(5), 1343-1351 (2019)
6. Watanabe T., Inoue, E., Mori, H., Osawa, Y., Okazaki, K., Delayed-onset enzootic bovine leukosis possibly caused by superinfection with bovine leukemia virus mutated in the pol gene., Arch. Virol. DOI: 10.1007/s00705-015-2457-4 (2015)
7. Inoue E., Matsumura K., Soma N., Hirasawa S., Wakimoto M., Arakaki Y., Yoshida T., Osawa Y., Okazaki K., L233P mutation of the Tax protein strongly correlated with leukemogenicity of bovine leukemia virus., Vet. Microbiol.167, 364-371 (2013)
8. Inoue E., Matsumura K., Maekawa K., Nagatsuka K., Nobuta M., Hirata M., Minagawa A., Osawa Y., Okazaki K., Genetic heterogeneity among bovine leukemia viruses in Japan and its relationship to leukemogenicity., Arch. Virol. 156, 1137-1141 (2011)
9. Matsumura K., Inoue E., Osawa Y., Okazaki K., Molecular epidemiology of bovine leukemia virus associated with enzootic bovine leukosis in Japan., Virus Res. 155, 343-348 (2011)

②ウイルス性人獣共通感染症の疫学調査と抗インフルエンザ薬の開発

　本学内科クリニックと共同で、インフルエンザウイルス流行株の遺伝子解析を行っている。2009年のパンデミックでは、本学の流行状況を分子レベルで明らかにした。また、自然界におけるインフルエンザウイルスの生態を明らかにするため、野鳥における疫学調査を実施している。

1. Fujii Y., Masatani T., Nishiyama S., Okajima M., Izumi F., Okazaki K.,Sakoda Y., Takada A., Ozawa M., Sugiyama M., Ito N.,Molecular characterisation of a novel Avian rotavirus A strain detected from a gull species (Larus sp.)., J Gen Virol, 103(10), (2022)
2. Kodama F., YamaguchiH., Park E., Tatemoto K., Sashika M., Nakao R., Terauchi Y., Mizuma K., Orba Y., Kariwa H., Hagiwara K., Okazaki K., Goto A., Komagome R., Miyoshi M., Ito T., Yamano K., Yoshii K., Funaki C., Ishizuka M., Shigeno A., Itakura Y., Bell-Sakyi L., Edagawa S., Nagasaka A., Sakoda Y., Sawa H., Maeda K., Saijo M., MatsunoK., A novel nairovirus associated with acute febrile illness in Hokkaido, Japan., Nat Commun, 12(1), (2021)
3. Torii S., Matsuno K., Qiu Y., Mori-Kajihara A., Kajihara M., Nakao R., Nao N., Okazaki K., Sashika M., Hiono T., Okamatsu M., Sakoda Y., Ebihara H., Takada A., Sawa H., Infection of newly identified phleboviruses in ticks and wild animals in Hokkaido, Japan indicating tick-borne life cycles., Ticks Tick Borne Dis, 10(2), 328-335 (2019) IF=3.817
4. Inoue E., Ieko M., Takahashi N., Osawa Y., Okazaki K., An NA-deficient 2009 pandemic H1N1 influenza virus mutant can efficiently replicate in cultured cells., Arch. Virol. 159, 797-800 (2013)
5. Inoue E., Ieko M., Takahashi N., Osawa Y., Okazaki K., Phylogenetic analyses of pandemic influenza A (H1N1) virus in university students at Tobetsu, Hokkaido, Japan., Microbiol. Immunol., 56, 273-279 (2012)
6. Inoue E., Wang X., Osawa Y., Okazaki K., Full genomic amplification and subtyping of influenza A virus using a single set of universal primers., Microbiol. Immunol., 54, 129-134 (2010)
7. Liu J., Okazaki K., Bai G., Shi W., Mweene, A. S., Kida, H., Interregional transmission of the internal protein genes of H2 subtype influenza virus in migratory ducks from North America to Eurasia., Virus Genes, 29, 81-86 （2004）
8. Liu J., Okazaki K., Shi W., Kida H., Phylogenetic analysis of hemagglutinin and neuraminidase genes of H9N2 viruses isolated from migratory ducks., Virus Genes, 27, 291-296 (2003)
9. Liu J., Okazaki K., Shi W., Wu Q., Mweene A.S., Kida. H., Phylogenetic analysis of neuraminidase gene of H9N2 influenza viruses prevalent in chickens in China during 1995-2002.. Virus Genes. 27, 197-202. （2003）
10. Liu J., Okazaki K., Ozaki H., Sakoda Y., Wu Q., Chen F., Kida H., H9N2 influenza viruses prevalent in poultry in China are phylogenetically distinct from A/quail/Hong Kong/G1/97 presumed to be the donor of the internal protein genes of the H5N1 Hong Kong/97 virus., Avian Pathol., 32, 551-560 (2003)
11. Okazaki K., Takada A., Ito T., Imai M., Takakuwa H., Hatta M., Ozaki H., Tanizaki T., Nagano T., Ninomiya A., Demenev V. A., Tyaptirganov M.M., Karatayeva T.D., Yamnikova S.S., Lvov D.K., Kida H., Precursor genes of future pandemic influenza viruses are perpetuated in ducks nesting in Siberia., Arch. Virol., 145, 885-893 (2000)

エゾシカにおけるE型肝炎ウイルスの血清疫学調査を実施し、エゾシカが本ウイルスに感染している可能性を示した。

1. Tomiyama D., Inoue E., Osawa Y., Okazaki K., Serological evidence of infection with hepatitis E virus among wild Yezo-deer, Cervus nippon yesoensis, in Hokkaido, Japan., J. Viral Hepat. 16, 524-528 （2009）

③抗ヘルペス薬の開発

　新規抗ヘルペス薬の開発をめざし、ヘルペスウイルス糖タンパク質の構造と機能を調べた。そのなかで、gB糖タンパク質内のαへリックス構造を形成するペプチドにウイルスの細胞内侵入阻害活性を見いだし、新規抗ヘルペス薬のシードを提供した。

1. Okazaki, K. Proteolytic cleavage of glycoprotein B is dispensable for in vitro replication but required for syncytium formation of pseudorabies virus. J. Gen. Virol. 88, 1859-1865　(2007)
2. Okazaki, K., Fujii, S., Takada, A., Kida, H. The amino-terminal residue of glycoprotein B is critical for neutralization of bovine herpesvirus 1. Virus Res. 115, 105-111　(2006)
3. Okazaki, K., Kida, H. A synthetic peptide from a heptad repeat region of herpesvirus glycoprotein B inhibits virus replication. J. Gen. Virol. 85, 2131-2137　(2004)