Molecular basis for the regulation of gene mutation rate in influenza viruses

• Project/Area Number: 26670227
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Virology
• Research Institution: Kagoshima University
• Principal Investigator: Ozawa Makoto 鹿児島大学, 農水産獣医学域獣医学系, 准教授 (50568722)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: インフルエンザウイルス / 遺伝子変異率 / 分子基盤 / ウイルスライブラリー

Outline of Final Research Achievements

To determine the molecular basis for the regulation of gene mutation rate in influenza A viruses, we generated recombinant influenza A virus library possessing random mutation(s) in the PB1 gene. We selected virus clones exhibiting (1) reduced sensitivity to antiviral and (2) enhanced stability of the reporter gene expression. Through validation of the mutation rate of the selected virus clones by means of reporter assays and sequencing of the PB1 genes, we identified the PB1 gene mutations that enhance and reduce the viral mutation rates, respectively.

Research Products

• [Journal Article] Contribution of the interaction between the rabies virus P protein and I-kappa B kinase e; to the inhibition of type I IFN induction signalling. (2016)
  • Author(s): Masatani T, Ozawa M, Yamada K, Ito N, Horie M, Matsuu A, Okuya K, Tsukiyama-Kohara K, Sugiyama M, Nishizono A.
  • Journal Title: J Gen Virol. Volume: 97 Issue: 2 Pages: 316-326
  • DOI: 10.1099/jgv.0.000362
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Amino acid changes in PB2 and HA affect the growth of a recombinant influenza virus expressing a fluorescent reporter protein (2016)
  • Author(s): H. Katsura, S. Fukuyama, S. Watanabe, M. Ozawa, G. Neumann, Y. Kawaoka
  • Journal Title: Sci Rep Volume: 6 Issue: 1 Pages: 19933-19933
  • DOI: 10.1038/srep19933
  • Peer Reviewed / Open Access
• [Journal Article] IRES-mediated translation of foot-and-mouth disease virus (FMDV) in cultured cells derived from FMDV-susceptible and -insusceptible animals (2016)
  • Author(s): T. Kanda, M. Ozawa, K. Tsukiyama-Kohara
  • Journal Title: BMC Vet Res Volume: 12 Issue: 1 Pages: 66-66
  • DOI: 10.1186/s12917-016-0694-8
  • Peer Reviewed / Open Access
• [Journal Article] Efficient isolation of Swine influenza viruses by age-targeted specimen collection. (2015)
  • Author(s): Ozawa M, Matsuu A, Yonezawa K, Igarashi M, Okuya K, Kawabata T, Ito K, Tsukiyama-Kohara K, Taneno A, Deguchi E.
  • Journal Title: J Clin Microbiol. 2015 Apr;53(4):1331-8. Volume: 53 Issue: 4 Pages: 1331-1338
  • DOI: 10.1128/jcm.02941-14
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Genetic diversity of highly pathogenic H5N8 avian influenza viruses at a single overwintering site of migratory birds in Japan, 2014/15 (2015)
  • Author(s): M. Ozawa, A. Matsuu, K. Tokorozaki, M. Horie, T. Masatani, H. Nakagawa, K. Okuya, T. Kawabata, S. Toda
  • Journal Title: Euro Surveill Volume: 20 Pages: 15-27
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Identification of mammalian-adapting mutations in the polymerase complex of an avian H5N1 influenza virus (2015)
  • Author(s): A. S. Taft, M. Ozawa, A. Fitch, J. V. Depasse, P. J. Halfmann, L. Hill-Batorski, M. Hatta, T. C. Friedrich, T. J. Lopes, E. A. Maher, E. Ghedin, C. A. Macken, G. Neumann, Y. Kawaoka
  • Journal Title: Nat Commun Volume: 6 Issue: 1 Pages: 7491-7491
  • DOI: 10.1038/ncomms8491
  • Peer Reviewed / Open Access
• [Journal Article] Genetic and serological surveillance for non-primate hepacivirus in horses in Japan (2015)
  • Author(s): Aya Matsuu, Seiji Hobo, Kunihide Ando, Takashi Sanekata, Fumio Sato, Yoshiro Endo, Tomohiko Amaya, Tomohiro Osaki, Masayuki Horie, Tatsunori Masatani, Makoto Ozawa, Kyoko Tsukiyama-Kohara
  • Journal Title: Veterinary Microbiology Volume: 179 Issue: 3-4 Pages: 219-227
  • DOI: 10.1016/j.vetmic.2015.05.028
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Molecular Determinants of Virulence and Stability of a Reporter-Expressing H5N1 Influenza A Virus. (2015)
  • Author(s): Zhao D, Fukuyama S, Yamada S, Lopes TJ, Maemura T, Katsura H, Ozawa M, Watanabe S, Neumann G, Kawaoka Y.
  • Journal Title: Journal of virology Volume: 89(22) Issue: 22 Pages: 11337-11346
  • DOI: 10.1128/jvi.01886-15
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] A Bivalent Vaccine Based on a PB2-Knockout Influenza Virus Protects Mice From Secondary Pneumococcal Pneumonia. (2015)
  • Author(s): Uraki R, Piao Z, Akeda Y, Iwatsuki-Horimoto K, Kiso M, Ozawa M, Oishi K, Kawaoka Y.
  • Journal Title: J Infect Dis Volume: 212 Issue: 12 Pages: 1939-1948
  • DOI: 10.1093/infdis/jiv341
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Isolation and characterization of influenza A viruses from environmental water at an overwintering site of migratory birds in Japan. (2015)
  • Author(s): Okuya K, Kawabata T, Nagano K, Tsukiyama-Kohara K, Kusumoto I, Takase K, Ozawa M.
  • Journal Title: Arch Virol. Volume: 160 Issue: 12 Pages: 3037-3052
  • DOI: 10.1007/s00705-015-2610-0
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Full genome sequences of torque teno sus virus strains that coinfected a pig with postweaning multisystemic wasting syndrome in Japan: implications for genetic diversity. (2015)
  • Author(s): Ozawa M, Kawabata T, Okuya K, Nagano K, Kanda T, Kanazawa N, Tsukiyama-Kohara K, Taneno A, Deguchi E.
  • Journal Title: Arch Virol. Volume: 160 Issue: 12 Pages: 3067-3074
  • DOI: 10.1007/s00705-015-2593-x
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Multi-spectral fluorescent reporter influenza viruses (Color-flu) as powerful tools for in vivo studies. (2015)
  • Author(s): Fukuyama S, Katsura H, Zhao D, Ozawa M, Ando T, Shoemaker JE, Ishikawa I, Yamada S, Neumann G, Watanabe S, Kitano H, Kawaoka Y.
  • Journal Title: Nature Communications Volume: 6 Issue: 1 Pages: 6600-6600
  • DOI: 10.1038/ncomms7600
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] A recombinant influenza virus vaccine expressing the F protein of respiratory syncytial virus (2014)
  • Author(s): W. Fonseca, M. Ozawa, M. Hatta, E. Orozco, M. B. Martinez, Y. Kawaoka
  • Journal Title: Arch Virol Volume: 159 Issue: 5 Pages: 1067-77
  • DOI: 10.1007/s00705-013-1932-z
  • Peer Reviewed
• [Journal Article] Recent insights into hepatitis B virus-host interactions. (2014)
  • Author(s): Ezzikouri S, Ozawa M, Kohara M, Elmdaghri N, Benjelloun S, Tsukivama-Kohara K.
  • Journal Title: Journal of Medical Virology Volume: 86 Issue: 6 Pages: 925-32
  • DOI: 10.1002/jmv.23916
  • Peer Reviewed / Open Access
• [Journal Article] Detection sensitivity of influenza rapid diagnostic tests (2014)
  • Author(s): Sakai-Tagawa Y, Ozawa M, Yamada S, Uchida Y, Saito T, Takahashi K, Sugaya N, Tashiro M, Kawaoka Y
  • Journal Title: Microbiol Immunol Volume: 58 Pages: 600-606
  • NAID: 40020235032
  • Peer Reviewed
• [Journal Article] Hemozoin as a novel adjuvant for inactivated whole virion influenza vaccine. (2014)
  • Author(s): Uraki R, Das SC, Hatta M, Kiso M, Iwatsuki-Horimoto K, Ozawa M, Coban C, Ishii KJ, Kawaoka Y.
  • Journal Title: Vaccine Volume: 32(41) Issue: 41 Pages: 5295-5300
  • DOI: 10.1016/j.vaccine.2014.07.079
  • Peer Reviewed / Open Access
• [Presentation] Characterization of porcine epidemic diarrhea (PED) virus field strains (2016)
  • Author(s): M. Ozawa
  • Organizer: International Symposium: Development of Effective PED and TGE vaccine and its application
  • Place of Presentation: Nigiwai Koryukan AU (Akita, Japan)
  • Year and Date: 2016-02-26
  • Int'l Joint Research / Invited
• [Presentation] 豚インフルエンザの現状 ～最新知見に基づくウイルス学的考察～ (2015)
  • Author(s): 小澤 真
  • Organizer: 平成27年度肝属獣医師会家畜衛生養豚部会研修会
  • Place of Presentation: ホテルさつき苑（鹿児島県鹿屋市）
  • Year and Date: 2015-10-01
  • Invited
• [Presentation] 2014-15年冬季に鹿児島県出水平野で分離されたH5N8亜型高病原性鳥インフルエンザウイルスの解析と感染野鳥における特徴 (2015)
  • Author(s): 松鵜 彩、所崎 香識、寸田 祐嗣、森田 剛仁、川口 博明、堀江 真行、正谷 達謄、中川 寛子、奥谷 公亮、川畑 淑子、戸田 重久、小原 恭子、小澤 真
  • Organizer: 第158回日本獣医学会学術集会
  • Place of Presentation: 北里大学（青森県十和田市）
  • Year and Date: 2015-09-07
• [Presentation] 渡り鳥から検出された新型ロタウイルスAの遺伝学的解析 (2015)
  • Author(s): 藤井 祐至、岡寺 康太、三竹 博道、伊藤 直人、岡田 和真、中川 賢人、岡崎 克則、迫田 義博、高田 礼人、小澤 真、正谷 達謄、杉山 誠
  • Organizer: 第158回日本獣医学会学術集会
  • Place of Presentation: 北里大学（青森県十和田市）
  • Year and Date: 2015-09-07
• [Presentation] I nfectious disease assessment in wild gorillas in African rainforest（ Gabon）： case of adenovirus (2015)
  • Author(s): Chimene Nze Nkogue、藤田 志歩、堀江 真行、Michiko Ogino、Yuki Kobayashi、Keijiro Mizukami、正谷 達謄、小澤 真、Alfred Ngomanda、Juichi Yamagiwa、大和 修、水谷 哲也、小原 恭子
  • Organizer: 第158回日本獣医学会学術集会
  • Place of Presentation: 北里大学（青森県十和田市）
  • Year and Date: 2015-09-07
• [Presentation] Efficient isolation of Swine influenza viruses by age-targeted specimen collection (2015)
  • Author(s): M. Ozawa, A. Matsuu, K. Yonezawa, M. Igarashi, K. Okuya, T. Kawabata, K. Ito, K. Tsukiyama-Kohara, A. Taneno, E. Deguchi
  • Organizer: The 7th International Symposium on Emerging and Re-emerging Pig Diseases 2015
  • Place of Presentation: Kyoto International Conference Center (Kyoto, Japan)
  • Year and Date: 2015-06-21
  • Int'l Joint Research
• [Presentation] Infectious experimental model of Neonatal Microminipig in ABSL2 Facility (2015)
  • Author(s): K. Akioka, H. Kawaguchi, K. Onoue, M. Ozawa, M. Horie, M. Noguchi, A. Tanimoto, N. Miyoshi
  • Organizer: The 7th International Symposium on Emerging and Re-emerging Pig Diseases 2015
  • Place of Presentation: Kyoto International Conference Center (Kyoto, Japan)
  • Year and Date: 2015-06-21
  • Int'l Joint Research
• [Presentation] Development of Microminipig infected model of porcine endemic diarrhea (PED) (2015)
  • Author(s): K. Onoue, H. Kawaguchi, M. Ozawa, M. Horie, K. Akioka, M. Noguchi, A. Tanimoto, N. Miyoshi
  • Organizer: The 7th International Symposium on Emerging and Re-emerging Pig Diseases 2015
  • Place of Presentation: Kyoto International Conference Center (Kyoto, Japan)
  • Year and Date: 2015-06-21
  • Int'l Joint Research
• [Presentation] 豚インフルエンザウイルスの効率的なサーベイランス方法の検討 (2014)
  • Author(s): 小澤 真、松鵜 彩、米澤 弘毅、五十嵐 学、奥谷 公亮、川畑 淑子、伊藤 公人、小原 恭子、種子野 章、出口 栄三郎
  • Organizer: 第62回日本ウイルス学会学術集会
  • Place of Presentation: パシフィコ横浜（横浜）
  • Year and Date: 2014-11-10 – 2014-11-12
• [Presentation] Development of Tupaia belangeri for HBV persistent infection (2014)
  • Author(s): Sayeh Ezzikouri、池 海英、真田 崇弘、永野 希織、山口 千穂、神田 雄大、金沢 伯弘、奥谷 公亮、上野 晃聖、中川 寛子、Nkogue, C.N.、三好 宣彰、小澤 真、Soumaya Benjelloum、村上 周子、田中 靖人、小原 道法、小原 恭子
  • Organizer: 第62回日本ウイルス学会学術集会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2014-11-10 – 2014-11-12
• [Presentation] 生体イメージングを用いたインフルエンザウイルスに対する宿主応答解析 (2014)
  • Author(s): 福山 聡、桂 廣亮、Dongming Zhao、安東 友美、Jason E. Shoemaker、小澤 真、河岡 義裕
  • Organizer: 第62回日本ウイルス学会学術集会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2014-11-10 – 2014-11-12
• [Presentation] インフルエンザワクチンに対するヘモゾインのアジュバンド効果の検証 (2014)
  • Author(s): 浦木 隆太、木曽 真紀、岩附（堀本） 研子、山吉 誠也、小澤 真、Coban Cevayir、石井 健、河岡 義裕
  • Organizer: 第62回日本ウイルス学会学術集会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2014-11-10 – 2014-11-12
• [Presentation] 亜型を超えた感染阻害活性を示すヘマグルチニン結合性特殊環状ペプチド (2014)
  • Author(s): 齊藤 誠、安井 文彦、棟方 翼、飛田 良美、小澤 真、小原 恭子、伊東 利紗、菅 裕明、佐々木 亨、窪田 規一、小原 道法
  • Organizer: 第62回日本ウイルス学会学術集会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2014-11-10 – 2014-11-12
• [Presentation] 家畜におけるインフルエンザ (2014)
  • Author(s): 小澤 真
  • Organizer: 平成26年度獣医学術九州地区学会
  • Place of Presentation: かごしま県民交流センター（鹿児島県鹿児島市）
  • Year and Date: 2014-10-04
  • Invited
• [Presentation] 豚トルクテノウイルスの遺伝的多様性 (2014)
  • Author(s): 小澤 真、川畑 淑子、奥谷 公亮、永野 希織、神田 雄大、金澤 伯弘、小原 恭子、出口 栄三郎
  • Organizer: 第157回日本獣医学会学術集会
  • Place of Presentation: 北海道大学（北海道札幌市）
  • Year and Date: 2014-09-09 – 2014-09-12
• [Presentation] ツルのインフルエンザウイルスに対する感受性の検討 (2014)
  • Author(s): 奥谷 公亮、川畑 淑子、永野 希織、小原 恭子、楠元 勇、高瀬 公三、小澤 真
  • Organizer: 第157回日本獣医学会学術集会
  • Place of Presentation: 北海道大学（北海道札幌市）
  • Year and Date: 2014-09-09 – 2014-09-12
• [Presentation] 全国の馬における非霊長類由来ヘパシウイルスの感染状況 (2014)
  • Author(s): 松鵜 彩、帆保 誠二、小澤 真、堀江 真行、正谷 達謄、佐藤 文夫、遠藤 祥郎、安藤 邦英、藤井 良和、天谷 友彦、小原 恭子
  • Organizer: 第157回日本獣医学会学術集会
  • Place of Presentation: 北海道大学（北海道札幌市）
  • Year and Date: 2014-09-09 – 2014-09-12
• [Presentation] Infectious disease assessment in wild gorillas in African rainforest（ Gabon）: case of adenovirus (2014)
  • Author(s): Nkogue, C.N.、藤田 志歩、荻野 倫子 、水上 圭二郎、正谷 達謄、小澤 真、堀江 真行、Ngomanda, A、山極 寿一 、大和 修、水谷 哲也、小原 恭子
  • Organizer: 第157回日本獣医学会学術集会
  • Place of Presentation: 北海道大学（北海道札幌市）
  • Year and Date: 2014-09-09 – 2014-09-12
• [Presentation] ツパイを用いたHCV感染・発症モデル系並びに治療評価系の開発 (2014)
  • Author(s): 池 海英、Ezzikouri, S.、真田 崇弘、永野 希織、山口 千穂、神田 雄大、金澤 伯弘、奥谷 公亮、上野 晃聖、中川 寛子、Nkogue, C.N.、小澤 真、小原 道法、小原 恭子
  • Organizer: 第51回日本ウイルス学会九州支部総会
  • Place of Presentation: 城山観光ホテル（鹿児島県鹿児島市）
  • Year and Date: 2014-09-05 – 2014-09-06
• [Presentation] 豚流行性下痢(PED)の制圧へ向けて (2014)
  • Author(s): 小澤 真
  • Organizer: 鹿屋市豚流行性下痢対策会議
  • Place of Presentation: 鹿屋市役所（鹿児島県鹿屋市）
  • Year and Date: 2014-08-07
  • Invited
• [Presentation] A bivalent vaccine based on a replication-incompetent influenza A virus possessing pneumococcal surface protein A protects mice from secondary pneumococcal infection (2014)
  • Author(s): Ryuta Uraki, Zhenyu Piao, Yukihiro Akeda, Kiyoko Iwatsuki-Horimoto, Maki Kiso, Makoto Ozawa, Kazunori Oishi, Yoshihiro Kawaoka
  • Organizer: XVI International Congress of Virology
  • Place of Presentation: Montreal's Convention Centre（モントリオール・カナダ）
  • Year and Date: 2014-07-27 – 2014-08-01