Amino acid mutations associated with growth ability of avian influenza viruses

• Project/Area Number: 24580441
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Basic veterinary science/Basic zootechnical science
• Research Institution: 独立行政法人医薬基盤研究所
• Principal Investigator: YAMADA Hiroshi 独立行政法人医薬基盤研究所, 創薬基盤研究部, 研究員 (30343304)
• Co-Investigator(Kenkyū-buntansha): OKAMOTO Shigefumi 独立行政法人医薬基盤研究所, 創薬基盤研究部, プロジェクトリーダー (50311759)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 鳥インフルエンザウイルス / 増殖能 / 鳥インフルエンザ

Outline of Final Research Achievements

We incubated three avian influenza viruses, H8N4, H10N2, and H12N5, in MDCK canine cells and got each mutated virus which had the ability to grow over 100-times better than parental one. We analyzed all nucleotide sequences of parental and mutated viruses. By making reassortants between parental and mutated viruses, it was found that PB2 and HA was responsible for increased growth ability. All three viruses had mutations in PB2 and HA. By making reassortants with a single mutation found in PB2 and HA, we identified mutations associated increased growth ability. A mutation in PB2 increased viral polymerase activity. Mutations in HA increased viral fusion activity after endocytosis.

Research Products

• [Journal Article] Dextran sulfate-resistant A/Puerto Rico/8/34 influenza virus is associated with the emergence of specific mutations in the neuraminidase glycoprotein (2014)
  • Author(s): Yamada H, Nagao C, Haredy AM, Mori Y, Mizuguchi K, Yamanishi K, Okamoto S
  • Journal Title: Antiviral Research Volume: 111 Pages: 69-77
  • DOI: 10.1016/j.antiviral.2014.09.002
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Neuraminidase gene homology contributes to the protective activity of influenza vaccines prepared from the influenza virus library (2014)
  • Author(s): Haredy AM, Yamada H, Sakoda Y, Okamatsu M, Yamamoto N, Omasa T, Mori Y, Kida H, Okamoto S, Okuno Y, Yamanishi K
  • Journal Title: Journal of General Virology Volume: 95 Issue: 11 Pages: 2365-2371
  • DOI: 10.1099/vir.0.067488-0
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] MDCK cell cultre-derived formalin-inactivated influenza whole virion vaccine from an influenza virus library conferred cross-protective immunity by intranasal administration in mice (2013)
  • Author(s): Haredy AM, et al.
  • Journal Title: Clinical and Vaccine Immunology Volume: 20 Issue: 7 Pages: 998-1007
  • DOI: 10.1128/cvi.00024-13
  • Peer Reviewed
• [Journal Article] Influenza virus neuraminidase contributes to the dextran sulfate-dependent suppressive replication of some influenza A virus strains. (2012)
  • Author(s): Yamada H, Moriishi E, Haredy AM, Takenaka N, Mori Y, Yamanishi K, Okamoto S.
  • Journal Title: Antiviral Research Volume: 96 Issue: 3 Pages: 344-352
  • DOI: 10.1016/j.antiviral.2012.09.012
  • Peer Reviewed
• [Presentation] Dextran sulfate による PR8 NA の機能阻害の解析 (2013)
  • Author(s): 山田博司、Ahmad M. Haredy、森康子、山西弘一、岡本成史
  • Organizer: 第27回インフルエンザ研究者交流の会シンポジウム
  • Place of Presentation: 北海道札幌市
• [Presentation] Impact of heterologus NA on inactivated whole virion vaccine (2013)
  • Author(s): Ahmad M. Haredy、山田博司、迫田義博、森 康子、喜田 宏、山西弘一、岡本成史
  • Organizer: 第27回インフルエンザ研究者交流の会シンポジウム
  • Place of Presentation: 北海道札幌市
• [Presentation] Dextran sulfate によるインフルエンザウイルス増殖の阻害とNA活性抑制との関連性 (2013)
  • Author(s): 山田博司、Ahmad M. Haredy、森康子、山西弘一、岡本成史
  • Organizer: 第61回日本ウイルス学会学術集会
  • Place of Presentation: 兵庫県神戸市
• [Presentation] NA subtype impact on influenza intranasal inactivated whole virion vaccine (2013)
  • Author(s): Ahmad M. Haredy、山田博司、迫田義博、森 康子、喜田 宏、山西弘一、岡本成史
  • Organizer: 第61回日本ウイルス学会学術集会
  • Place of Presentation: 兵庫県神戸市
• [Presentation] Dextran sulfateによるインフルエンザウイルスNA活性とウイルス増殖の阻害 (2012)
  • Author(s): 山田博司、Ahmad M. Haredy、森康子、山西弘一、岡本成史
  • Organizer: 第26回インフルエンザ研究者交流の会シンポジウム
  • Place of Presentation: 福島県
• [Presentation] Dextran sulfate によるインフルエンザウイルス増殖の阻害とNA活性抑制との関連性 (2012)
  • Author(s): 山田博司、Ahmad M. Haredy、森康子、山西弘一、岡本成史
  • Organizer: 第60回日本ウイルス学会学術集会
  • Place of Presentation: 大阪府
• [Presentation] パンデミックインフルエンザの発生に即応した、ワクチン製造用種ウイルス株の作出―インフルエンザウイルスライブラリーの利用― (2012)
  • Author(s): 岡本成史、竹中延之、迫田義博、岡松正敏、山本直樹、Haredy, AM, 山田博司、森 康子、喜田 宏、山西弘一
  • Organizer: 第60回日本ウイルス学会学術集会
  • Place of Presentation: 大阪府