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Research of drug-resistant mechanism in highly pathogenic avian influenza virus

Research Project

Project/Area Number 20590118
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Environmental pharmacy
Research InstitutionThe University of Tokyo

Principal Investigator

TAGAWA Yuko  The University of Tokyo, 医科学研究所, 助手 (40178538)

Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2010: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2009: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2008: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Keywords高病原性鳥インフルエンザウイルス / 薬剤耐性 / 抗インフルエンザ薬 / 迅速診断 / 病原性 / 鳥インフルエンザウイルス / オセルタミビル / 国際情報交換 / ベトナム:インドネシア / 抗ウイルス剤
Research Abstract

The persistence of H5N1 avian influenza viruses in many Asian countries and their ability to cause fatal infections in humans have raised serious concerns about a global flu pandemic. We obtained important results as below :
(1) Oseltamivir-resistant H5N1 viruses have been isolated from oseltamivir-treated patients. The investigational drug T-705 has effectively protects mice from lethal infection with these viruses.
(2) H5N1 viruses have been transmitted to pigs on multiple occasions in Indonesia.
(3) A direct analysis of the viral RNAs of H5N1 viruses in patients revealed that efficient virus propagation in the human. Viruses grown in culture or eggs did not always reflect those in patients.
(4) Many influenza rapid diagnostic tests are available for the detection of H5N1 influenza virus infections.

Report

(4 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (41 results)

All 2011 2010 2009 2008 Other

All Journal Article (29 results) (of which Peer Reviewed: 29 results) Presentation (9 results) Remarks (3 results)

  • [Journal Article] Sero-prevalence of Pandemic (H1N1) 2009 Influenza A Virus among Schoolchildren and Their Parents in Tokyo, Japan2011

    • Author(s)
      Iwatsuki-Horimoto K, Horimoto T, Tamura D, Kiso M, Kawakami E, Hatakeyama S, Ebihara Y, Koibuchi T, Fujii T, Takahashi K, Shimojima M, Sakai-Tagawa Y, Ito M, Sakabe S, Iwasa A, Takahashi K, Ishii T, Gorai T, Tsuji K, Iwamoto A, Kawaoka Y
    • Journal Title

      Clin Vaccine Immunol.

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Sero-prevalence of Pandemic (H1N1) 2009 Influenza A Virus among Schoolchildren and Their Parents in Tokyo, Japan.2011

    • Author(s)
      Iwatsuki-Horimoto K, 他20名
    • Journal Title

      Clin Vaccine Immunol.

      Volume: (in press)

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Influenza A (H5N1) viruses from pigs, Indonesia2010

    • Author(s)
      Nidom CA, Takano R, Yamada S, Sakai-Tagawa Y, Daulay S, Aswadi D, Suzuki T, Suzuki Y, Shinya K, Iwatsuki-Horimoto K, Muramoto Y, Kawaoka Y
    • Journal Title

      Emerg Infect Dis. 16(10)

      Pages: 1515-23

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] The HA and NS genes of human H5N1 influenza A virus contribute to high virulence in ferrets2010

    • Author(s)
      Imai H, Shinya K, Takano R, Kiso M, Muramoto Y, Sakabe S, Murakami S, Ito M, Yamada S, Le MT, Nidom CA, Sakai-Tagawa Y, Takahashi K, Omori Y, Noda T, Shimojima M, Kakugawa S, Goto H, Iwatsuki-Horimoto K, Horimoto T, Kawaoka Y
    • Journal Title

      PLoS Pathog 6(9)

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Biological and structural characterization of a host-adapting amino acid in influenza virus2010

    • Author(s)
      Yamada S, Hatta M, Staker BL, Watanabe S, Imai M, Shinya K, Sakai-Tagawa Y, Ito M, Ozawa M, Watanabe T, Sakabe S, Li C, Kim JH, Myler PJ, Phan I, Raymond A, Smith E, Stacy R, Nidom CA, Lank SM, Wiseman RW, Bimber BN, O'Connor DH, Neumann G, Stewart LJ, Kawaoka Y
    • Journal Title

      PLoS Pathog 6(8)

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Pathogenicity of highly pathogenic avian H5N1 influenza A viruses isolated from humans from 2003 to 2008 in Northern Vietnam2010

    • Author(s)
      Le QM, Ito M, Muramoto Y, Hoang PV, Vuong CD, Sakai-Tagawa Y, Kiso M, Ozawa M, Takano R, Kawaoka Y
    • Journal Title

      J Gen Virol. 91(Pt 10)

      Pages: 2485-90

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Sensitivity of influenza rapid diagnostic tests to H5N1 and 2009 pandemic H1N1 viruses2010

    • Author(s)
      Sakai-Tagawa Y, Ozawa M, Tamura D, Le MQ, Nidom CA, Sugaya N, Kawaoka Y
    • Journal Title

      J Clin Microbiol. 48(8)

      Pages: 2872-7

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Significance of seasonal influenza viruses in the stool of pediatric patients2010

    • Author(s)
      Tamura D, Fujino M, Ozawa M, Iwatsuki-Horimoto K, Goto H, Sakai-Tagawa Y, Horimoto T, Nirasawa M, Kawaoka Y
    • Journal Title

      Pediatr Infect Dis J. 29(6)

      Pages: 578-9

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] T-705 (favipiravir) activity against lethal H5N1 influenza A viruses2010

    • Author(s)
      Kiso M, Takahashi K, Sakai-Tagawa Y, Shinya K, Sakabe S, Le QM, Ozawa M, Furuta Y, Kawaoka Y
    • Journal Title

      Proc Natl Acad Sci U S A 107(2)

      Pages: 882-7

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Mutations in influenza A virus during amantadine-oseltamivir combination therapy2010

    • Author(s)
      Shiraishi K, Mitamura K, Ozawa M, Kakugawa S, Kiso M, Sakai-Tagawa Y, Sugaya N, Kawaoka Y
    • Journal Title

      Pediatr Infect Dis J 5

      Pages: 243-248

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Influenza A (H5N1) viruses from pigs, Indonesia.2010

    • Author(s)
      Nidom CA, 他11名
    • Journal Title

      Emerg Infect Dis

      Volume: 16(10) Pages: 1515-1523

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The HA and NS genes of human H5N1 influenza A virus contribute to high virulence in ferrets.2010

    • Author(s)
      Imai H, 他20名
    • Journal Title

      PLoS Pathog

      Volume: 6(9)

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Biological and structural characterization of a host-adapting amino acid in influenza virus.2010

    • Author(s)
      Yamada S, 他25名
    • Journal Title

      PLoS Pathog.

      Volume: 6(8)

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Pathogenicity of highly pathogenic avian H5N1 influenza A viruses isolated from humans from 2003 to 2008 in Northern Vietnam.2010

    • Author(s)
      Le QM, 他9名
    • Journal Title

      J Gen Virol.

      Volume: 91 Pages: 2485-2490

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Sensitivity of influenza rapid diagnostic tests to H5N1 and 2009 pandemic H1N1 viruses.2010

    • Author(s)
      Sakai-Tagawa Y, 他6名
    • Journal Title

      J Clin Microbiol.

      Volume: 48(8) Pages: 2872-2877

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Significance of seasonal influenza viruses in the stool of pediatric patients.2010

    • Author(s)
      Tamura D, 他8名
    • Journal Title

      Pediatr Infect Dis J

      Volume: 29(6) Pages: 578-579

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Ostrich involvement in the selection of H5N1 influenza virus possessing mammalian-type amino acids in the PB2 protein2009

    • Author(s)
      Shinya K, Makino A, Ozawa M, Kim JH, Sakai-Tagawa Y, Ito M, Le QM, Kawaoka Y
    • Journal Title

      J Virol 83(24)

      Pages: 13015-8

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] In vitro and in vivo characterization of new swine-origin H1N1 influenza viruses2009

    • Author(s)
      Itoh Y, Shinya K, Kiso M, Watanabe T, Sakoda Y, Hatta M, Muramoto Y, Tamura D, Sakai-Tagawa Y, Noda T, Sakabe S, Imai M, Hatta Y, Watanabe S, Li C, Yamada S, Fujii K, Murakami S, Imai H, Kakugawa S, Ito M, Takano R, Iwatsuki-Horimoto K, Shimojima M, Horimoto T, Goto H, Takahashi K, Makino A, Ishigaki H, Nakayama M, Okamatsu M, Takahashi K, Warshauer D, Shult PA, Saito R, Suzuki H, Furuta Y, Yamashita M, Mitamura K, Nakano K, Nakamura M, Brockman-Schneider R, Mitamura H, Yamazaki M, Sugaya N, Suresh M, Ozawa M, Neumann G, Gern J, Kida H, Ogasawara K, Kawaoka Y
    • Journal Title

      Nature 460(7258)

      Pages: 1021-5

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Phylogenetic characterization of H5N1 avian influenza viruses isolated in Indonesia from 2003-20072009

    • Author(s)
      Takano R, Nidom CA, Kiso M, Muramoto Y, Yamada S, Sakai-Tagawa Y, Macken C, Kawaoka Y
    • Journal Title

      Virology 390(1)

      Pages: 13-21

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] A comparison of the pathogenicity of avian and swine H5N1 influenza viruses in Indonesia2009

    • Author(s)
      Takano R, Nidom CA, Kiso M, Muramoto Y, Yamada S, Shinya K, Sakai-Tagawa Y, Kawaoka Y
    • Journal Title

      Arch Virol 154(4)

      Pages: 677-81

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Selection of H5N1 influenza virus PB2 during replication in humans2009

    • Author(s)
      Le QM, Sakai-Tagawa Y, Ozawa M, Ito M, Kawaoka Y
    • Journal Title

      J Virol 83(10)

      Pages: 5278-81

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] T-705(favipiravir)activity against lethal H5N1 influenza A viruses.2009

    • Author(s)
      Kiso M., 他7名
    • Journal Title

      Proc Natl Acad Sci USA. 107(2)

      Pages: 882-887

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Ostrich involvement in the selection of H5N1 influenza virus possessing mammalian-type amino acids in the PB2 protein.2009

    • Author(s)
      Shinya K., 他7名
    • Journal Title

      J Virol. 83(24)

      Pages: 13015-13018

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] In vitro and in vivo characterization of new swine-origin H1N1 influenza viruses.2009

    • Author(s)
      Itoh Y., 他51名
    • Journal Title

      Nature 460(7258)

      Pages: 1021-1025

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Phylogenetic characterization of H5N1 avian influenza viruses isolated in Indonesia from 2003-2007.2009

    • Author(s)
      Takano R., 他7名
    • Journal Title

      Virology 390(1)

      Pages: 13-21

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A comparison of the pathogenicity of avian and swine H5N1 influenza viruses in Indonesia2009

    • Author(s)
      Takano R., 他7名
    • Journal Title

      Arch Virol. 154(4)

      Pages: 677-681

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Selection of H5N1 influenza virus PB2 during replication in humans.2009

    • Author(s)
      Le Q.M., 他7名
    • Journal Title

      J Virol. 83(10)

      Pages: 5278-5281

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cross-clade protective immunity of H5N1 influenza vaccines in a mouse model2008

    • Author(s)
      Murakami S, Iwasa A, Iwatsuki-Horimoto K, Ito M, Kiso M, Kida H, Takada A, Nidom CA, Mai LQ, Yamada S, Imai H, Sakai-Tagawa Y, Kawaoka Y, Horimoto T
    • Journal Title

      Vaccine 26(50)

      Pages: 6398-404

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Cross-clade protective immunity of H5N1 influenza vaccines in a mouse model.2008

    • Author(s)
      Murakami S
    • Journal Title

      Vaccine. 26(2)

      Pages: 6398-6404

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Presentation] H5N1インフルエンザウイルス高病原性発揮のメカニズム2010

    • Author(s)
      今井博貴
    • Organizer
      第58回日本ウイルス学会学術集会
    • Place of Presentation
      徳島市あわぎんホール
    • Year and Date
      2010-11-08
    • Related Report
      2010 Final Research Report
  • [Presentation] H5N1インフルエンザウイルス高病原性発揮のメカニズム2010

    • Author(s)
      今井博貴, 他19名
    • Organizer
      第58回 日本ウイルス学会学術集会
    • Place of Presentation
      徳島市あわぎんホール
    • Year and Date
      2010-11-08
    • Related Report
      2010 Annual Research Report
  • [Presentation] Pathogenicity of highly-pathogenic avian H5N1 influenza A viruses isolated from humans during 2003 to 2008 in Northern Vietnam2010

    • Author(s)
      Le QM
    • Organizer
      Options for the Control of Influenza VII
    • Place of Presentation
      Hong Kong SAR,China
    • Related Report
      2010 Final Research Report
  • [Presentation] Pathogenicity of highly-pathogenic avian H5N1 influenza A viruses isolated from humans during 2003 to 2008 in Northern Vietnam2010

    • Author(s)
      Le QM, 他9名
    • Organizer
      Options for the Control of Influenza VII
    • Place of Presentation
      Hong Kong SAR, China
    • Related Report
      2010 Annual Research Report
  • [Presentation] 感染患者体内におけるH5N1鳥インフルエンザウイルスの変異2008

    • Author(s)
      坂井(田川)優子
    • Organizer
      第56回日本ウイルス学会学術集会
    • Place of Presentation
      岡山コンベンションセンター
    • Year and Date
      2008-10-28
    • Related Report
      2010 Final Research Report 2008 Annual Research Report
  • [Presentation] 高病原性H5N1鳥インフルエンザウイルスのサルにおける病原性の比較2008

    • Author(s)
      村本裕紀子
    • Organizer
      第56回日本ウイルス学会学術集会
    • Place of Presentation
      岡山コンベンションセンター
    • Year and Date
      2008-10-28
    • Related Report
      2010 Final Research Report
  • [Presentation] H5N1不活化インフルエンザワクチンのクレード間交差防御免疫能の解析2008

    • Author(s)
      村上晋
    • Organizer
      第56回日本ウイルス学会学術集会
    • Place of Presentation
      岡山コンベンションセンター
    • Year and Date
      2008-10-28
    • Related Report
      2010 Final Research Report
  • [Presentation] インドネシアのブタから分離されたH5N1インフルエンザウイルスの性状解析2008

    • Author(s)
      高野量
    • Organizer
      第56回日本ウイルス学会学術集会
    • Place of Presentation
      岡山コンベンションセンター
    • Year and Date
      2008-10-28
    • Related Report
      2010 Final Research Report
  • [Presentation] H5N1インフルエンザウイルスの正常ヒト呼吸器上皮細胞における増殖性に関与する変異2008

    • Author(s)
      山田晋也
    • Organizer
      第56回日本ウイルス学会学術集会
    • Place of Presentation
      岡山コンベンションセンター
    • Year and Date
      2008-10-28
    • Related Report
      2010 Final Research Report
  • [Remarks] ホームページ

    • URL

      http://www.ims.u-tokyo.ac.jp/virology/index.html

    • Related Report
      2010 Final Research Report
  • [Remarks]

    • URL

      http://www.ims.u-tokyo.ac.jp/virology/index.html

    • Related Report
      2010 Annual Research Report
  • [Remarks]

    • URL

      http://www.ims.u-tokyo.ac.jp/virology/index.html

    • Related Report
      2009 Annual Research Report

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Published: 2008-04-01   Modified: 2016-04-21  

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