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

高致病性流感病毒治疗研究的新策略和基本方法。

• 批准号: 21791015
• 负责人: KASHIWAGI Takahito
• 金额: $ 2.66万
• 依托单位: Kurume University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21791015/
• 关键词: 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

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.

甲型流感病毒可以感染多种不同的宿主，因此必须适应不同的宿主温度以进行有效的病毒复制。众所周知，PB2亚基参与温度敏感性。另一方面，PA亚基在热敏性中的作用仍然知之甚少。为了测试哪些聚合酶亚基参与了热应激，我们在核糖核蛋白（RNP）复合物中重建了流感RNA聚合酶的人工杂交体，并在不同温度下测量了mRNA、cRNA和vRNA的稳态水平。PA亚基参与调节热胁迫下RNP的活性。PA亚基的残基114是这种活性的重要决定因素。这些结果表明，甲型流感病毒可能通过RNA聚合酶基因的重排获得适应不同体温的RNA聚合酶。因此，我们为研究抗流感病毒的新药和治疗方法提供了新的途径。

项目成果

Clinical Study Concerning the Relationship between Community-Acquired Pneumonia and Viral Infection in Northern Thailand

• DOI: 10.2169/internalmedicine.50.4738
• 发表时间: 2011-01-01
• 期刊: INTERNAL MEDICINE
• 影响因子: 1.2
• 作者: Hara, Koyu;Yahara, Koji;Watanabe, Hiroshi
• 通讯作者: Watanabe, Hiroshi

Infection control for the pandemic(H1N1) 2009 in Kurume university hospital

久留米大学医院2009年H1N1流感大流行的感染控制

• 发表时间: 2010
• 作者: Watanabe H;Kashiwagi T;Hara K;Masunaga K;Kawano S;Miura M;Iwahashi J;Qin L;Imamura Y;and Hamada N.
• 通讯作者: and Hamada N.

The PA subunit of the influenza A virus RNA polymerase contributes its stable activity on thermal stress through the promoter binding

甲型流感病毒RNA聚合酶的PA亚基通过启动子结合贡献其对热应激的稳定活性

• 发表时间: 2011
• 作者: Kashiwagi T;Hara K;Hamada N and Watanabe H.
• 通讯作者: Hamada N and Watanabe H.

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-

甲型流感病毒RNA聚合酶亚基亚型之间的亲和力分析-关于PA(H3N2)的亲和力决定位点-

• 发表时间: 2010
• 作者: 原好勇;中園陽子;柏木孝仁;今村宜寛;濱田信之;渡邊浩
• 通讯作者: 渡邊浩

The N-terminal region of the PA subunit of influenza virus RNA polymerase contributes to the functional RNA formation

流感病毒 RNA 聚合酶 PA 亚基的 N 端区域有助于功能性 RNA 的形成

• 发表时间: 2010
• 作者: Hara K;Nakazono Y;Kashiwagi T;and Watanabe H.
• 通讯作者: and Watanabe H.