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Novel strategies and basic approaches for the study of the treatment against highly pathogenic influenza virus.

Research Project

Project/Area Number 21791015
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeSingle-year Grants
Research Field Pediatrics
Research InstitutionKurume University

Principal Investigator

KASHIWAGI Takahito  久留米大学, 医学部, 講師 (70320158)

Project Period (FY) 2009 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords小児感染症学 / ウイルス / 感染症 / 医療・福祉 / 微生物 / 小児科 / 呼吸器 / 内科
Research Abstract

Influenza A virus can infect a variety of different hosts and therefore has to adapt to different host temperatures for its efficient viral replication. It is well known that the PB2 subunit is involved in temperature sensitivity. On the other hand the role of the PA subunit in thermal sensitivity is still poorly understood. To test which polymerase subunit(s) were involved in thermal stress we reconstituted artificial hybrids of influenza RNA polymerase in ribonucleoprotein(RNP) complexes and measured steady-state levels of mRNA, cRNA and vRNA at different temperatures. The PA subunit was involved in modulating RNP activity under thermal stress. Residue 114 of the PA subunit was an important determinant of this activity. These findings suggested that influenza A virus may acquire an RNA polymerase adapted to different body temperatures of the host by reassortment of the RNA polymerase genes. Thus, we have introduced the new way to study novel drugs and treatments against influenza virus.

Report

(4 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (31 results)

All 2012 2011 2010 2009 Other

All Journal Article (8 results) (of which Peer Reviewed: 4 results) Presentation (19 results) Remarks (4 results)

  • [Journal Article] The RNA polymerase PB2 subunit of influenza A/HongKong/156/1997(H5N1) restricts the replication of reassortant ribonucleoprotein complexes ribonucleoprotein complexes2012

    • Author(s)
      Nakazono Y, Hara K, Kashiwagi T, Hamada N, and Watanabe H.
    • Journal Title

      PLoS ONE

      Volume: 7(2)

    • Related Report
      2011 Final Research Report
  • [Journal Article] The RNA polymerase PB2 subunit of influenza A/HongKong/156/1997 (H5N1) restricts the replication of reassortant ribonucleoprotein complexes2012

    • Author(s)
      Nakazono Y Hara K, Kashiwagi T, Hamada N, Watanabe H
    • Journal Title

      PLoS ONE

      Volume: 7(2) Issue: 2 Pages: e32634-e32634

    • DOI

      10.1371/journal.pone.0032634

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Clinical study concerning the relationship between community-acquired pneumonia and viral infection in northern Thailand2011

    • Author(s)
      Hara K, Yahara K, Gotoh K, Nakazono Y, Kashiwagi T, Imamura Y, Hamada N, Khositsakulchai W, Sanchai T, Khantawa B, Tharavichitkul P, Maneekarn N, Sirisanthana T, and Watanabe H.
    • Journal Title

      Intern Med

      Volume: 50 Pages: 991-998

    • NAID

      130000650101

    • Related Report
      2011 Final Research Report
  • [Journal Article] Clinical study concerning the relationship between community-acquired pneumonia and viral infection in northern Thailand2011

    • Author(s)
      Hara K, Yahara K, Gotoh K, Nakazono Y, Kashiwagi T, et al
    • Journal Title

      Inter.Med.

      Volume: 50 Pages: 991-998

    • NAID

      130000650101

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Artificial hybrids of influenza A virus RNA polymerase reveal PA subunit modulates its thermal sensitivity2010

    • Author(s)
      Kashiwagi T, Hara K, Nakazono Y, Hamada N, and Watanabe H.
    • Journal Title

      PLoS ONE

      Volume: 5(12)

    • Related Report
      2011 Final Research Report
  • [Journal Article] Artificial Hybrids of Influenza A Virus RNA Polymerase Reveal PA Sub unit Modulates Its Thermal Sensitivity2010

    • Author(s)
      柏木孝仁
    • Journal Title

      PLoS ONE

      Volume: 5(12)e15140 Pages: 1-11

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The N-terminal of the PA subunit of the RNA polymerase of influenza A/HongKong/156/97 influences promoter binding2009

    • Author(s)
      Kashiwagi T, Leung BW, Deng T, Chen H, and Brownlee GG.
    • Journal Title

      PLoS ONE

      Volume: 4(5)

    • Related Report
      2011 Final Research Report
  • [Journal Article] The N-terminal of the PA subunit of the RNA polymerase of influenza A/HongKong/156/97 influences promoter binding2009

    • Author(s)
      柏木孝仁
    • Journal Title

      PLoS ONE 4(5)e5473

      Pages: 1-11

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Presentation] The PA subunit of the influenza A virus RNA polymerase contributes its stable activity on thermal stress through the promoter binding2011

    • Author(s)
      Kashiwagi T, Hara K, Hamada N and Watanabe H.
    • Organizer
      15th US-Japan Acute Respiratory Infections Panel Meeting
    • Place of Presentation
      Wakayama, Japan
    • Year and Date
      2011-11-15
    • Related Report
      2011 Final Research Report
  • [Presentation] The PA subunit of the influenza A virus RNA polymerase contributes its stable activity on thermal stress through the promoter binding2011

    • Author(s)
      Kashiwagi T, Hara K, Hamada N, Watanabe H
    • Organizer
      United States-Japan Cooperative Medical Science Program. 15th US-Japan Acute Respiratory Infections Panel Meeting
    • Place of Presentation
      Wakayama, Japan
    • Year and Date
      2011-11-15
    • Related Report
      2011 Annual Research Report
  • [Presentation] Mutational analysis of the PB2 subunit of H5N1 influenza virus RNA polymerase required for the assembly of the functional hybrid ribonucleoprotein2011

    • Author(s)
      中園陽子、原好勇、柏木孝仁、濱田信之、渡邊浩
    • Organizer
      第15回国際ウイルス学会(15th International Congress of Virology)
    • Place of Presentation
      札幌
    • Year and Date
      2011-09-13
    • Related Report
      2011 Final Research Report
  • [Presentation] Inhibitory effect of human metapneumovirus (HMPV) M2-2 on RNA synthesis2011

    • Author(s)
      濱田信之、原好勇、中園陽子、柏木孝仁、渡邊浩
    • Organizer
      第15回国際ウイルス学会
    • Place of Presentation
      札幌
    • Year and Date
      2011-09-13
    • Related Report
      2011 Annual Research Report
  • [Presentation] Mutational analysis of the PB2 subunit of H5N1 influenza virus RNA polymerase required for the assembly of the functional hybrid ribonucleoprotein2011

    • Author(s)
      中園陽子、原好勇、柏木孝仁、濱田信之、渡邊浩
    • Organizer
      第15回国際ウイルス学会
    • Place of Presentation
      札幌
    • Year and Date
      2011-09-13
    • Related Report
      2011 Annual Research Report
  • [Presentation] オセルタミビル感受性株と抵抗性株がそれぞれ左右剖検肺から検出された新型インフルエンザウイルスA(H1N1/2009)のクローン解析2011

    • Author(s)
      濱田信之、今村豊、原好勇、柏木孝仁、今村宜寛、千々和勝己、渡邊浩
    • Organizer
      第85回日本感染症学会学術総会
    • Place of Presentation
      東京
    • Year and Date
      2011-04-22
    • Related Report
      2011 Annual Research Report
  • [Presentation] A型インフルエンザウイルス遺伝子複製酵素から見た温度への適応について2011

    • Author(s)
      柏木孝仁、原好勇、今村宜寛、濱田信之、渡邊浩
    • Organizer
      第85回日本感染症学会学術総会
    • Place of Presentation
      東京
    • Year and Date
      2011-04-21
    • Related Report
      2011 Annual Research Report 2011 Final Research Report
  • [Presentation] A型インフルエンザウイルス遺伝子複製酵素の亜型間親和性を決定するアミノ酸解析2011

    • Author(s)
      原好勇、柏木孝仁、渡邊浩
    • Organizer
      第85回日本感染症学会学術総会
    • Place of Presentation
      東京
    • Year and Date
      2011-04-21
    • Related Report
      2011 Annual Research Report 2011 Final Research Report
  • [Presentation] A型インフルエンザウイルスRNAポリメラーゼサブユニットの亜型間での親和性解析-PA(H3N2)の親和性決定部位について-2010

    • Author(s)
      原好勇、中園陽子、柏木孝仁、今村宜寛、濱田信之、渡邊浩
    • Organizer
      第58回日本ウイルス学会学術集会
    • Place of Presentation
      徳島
    • Year and Date
      2010-11-08
    • Related Report
      2011 Final Research Report
  • [Presentation] A型インフルエンザウイルスRNAポリメラーゼサブユニットの亜型間での親和性解析-PB2(H5N1)の親和性決定部位について-2010

    • Author(s)
      中園陽子、原好勇、柏木孝仁、今村宜寛、濱田信之、渡邊浩
    • Organizer
      第58回日本ウイルス学会学術集会
    • Place of Presentation
      徳島
    • Year and Date
      2010-11-07
    • Related Report
      2011 Final Research Report
  • [Presentation] A型インフルエンザウイルス遺伝子複製酵素の温度変化への適応2010

    • Author(s)
      柏木孝仁、原好勇、中園陽子、濱田信之、岩橋潤、今村宜寛、渡邊浩
    • Organizer
      第58回日本ウイルス学会学術集会
    • Place of Presentation
      徳島
    • Year and Date
      2010-11-07
    • Related Report
      2011 Final Research Report
  • [Presentation] The N-terminal region of the PA subunit of influenza virus RNA polymerase contributes to the functional RNA formation2010

    • Author(s)
      Hara K, Nakazono Y, Kashiwagi T, and Watanabe H.
    • Organizer
      Options for the Control of Influenza VII
    • Place of Presentation
      Hong Kong
    • Year and Date
      2010-09-04
    • Related Report
      2011 Final Research Report
  • [Presentation] PA subunit of Influenza A virus RNA polymerae is involved in the stable RNA replication at high temperature2010

    • Author(s)
      Kashiwagi T, Hara K, Nakazono Y, Hamada N, and Watanabe H.
    • Organizer
      Options for the Control of Influenza VII
    • Place of Presentation
      Hong Kong
    • Year and Date
      2010-09-04
    • Related Report
      2011 Final Research Report
  • [Presentation] Infection control for the pandemic(H1N1) 2009 in Kurume university hospital2010

    • Author(s)
      Watanabe H, Kashiwagi T, Hara K, Masunaga K, Kawano S, Miura M, Iwahashi J, Qin L, Imamura Y, and Hamada N.
    • Organizer
      Meeting of the global outbreak alert and response network(GOARN) partners from the western pacific region
    • Place of Presentation
      Siem Reap, Cambodia
    • Year and Date
      2010-03-23
    • Related Report
      2011 Final Research Report
  • [Presentation] A型インフルエンザウイルス遺伝子複製酵素の温度変化への適応2010

    • Author(s)
      柏木孝仁
    • Organizer
      第58回 日本ウイルス学会学術集会
    • Place of Presentation
      徳島
    • Related Report
      2010 Annual Research Report
  • [Presentation] PA subunit of influenza A virus RNA polymerase is involved in the stable RNA replication at the high temperature2010

    • Author(s)
      柏木孝仁
    • Organizer
      Options for the Control of Influenza VII
    • Place of Presentation
      香港、中華人民共和国
    • Related Report
      2010 Annual Research Report
  • [Presentation] Analysis of the hybrid trimeric complexes consisted of human and avian influenza virus RNA polymerase subunits2009

    • Author(s)
      Nakazono Y, Hara K, Kashiwagi T, and Watanabe H.
    • Organizer
      第32回日本分子生物学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2009-12-09
    • Related Report
      2011 Final Research Report
  • [Presentation] インフルエンザウイルス遺伝子複製酵素の研究2009

    • Author(s)
      柏木孝仁、原好勇、岩橋潤、中園陽子、今村宜寛、濱田信之
    • Organizer
      第57回日本ウイルス学会学術総会
    • Place of Presentation
      東京
    • Year and Date
      2009-10-26
    • Related Report
      2011 Final Research Report
  • [Presentation] インフルエンザウイルスPAサブユニットのN末端はプロモーターとの結合を通じてポリメラーゼの活性に影響を与えている2009

    • Author(s)
      柏木孝仁
    • Organizer
      第57回 日本ウイルス学会
    • Place of Presentation
      都市センターホテル(東京)
    • Related Report
      2009 Annual Research Report
  • [Remarks]

    • URL

      http://www.med.kurume-u.ac.jp/med/virol/index.html

    • Related Report
      2011 Final Research Report
  • [Remarks]

    • URL

      http://www.med.kurume-u.ac.jp/med/virol/

    • Related Report
      2011 Annual Research Report
  • [Remarks]

    • URL

      http://www.med.kurume-u.ac.jp/med/virol/

    • Related Report
      2010 Annual Research Report
  • [Remarks]

    • URL

      http://www.med.kurume-u.ac.jp/med/virol/

    • Related Report
      2009 Annual Research Report

URL: 

Published: 2009-04-01   Modified: 2016-04-21  

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