Control of genomic RNA replication by the nonstructural protein NS2 of influenza A virus.

甲型流感病毒非结构蛋白 NS2 控制基因组 RNA 复制。

• 批准号: 04670279
• 负责人: ODAGIRI Takato
• 金额: $ 1.28万
• 依托单位: Jichi Medical School
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1992
• 资助国家: 日本
• 起止时间: 1992 至 1993
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-04670279/
• 关键词: Influenza A virus; Nonstructural NS2; Replication, transcription; DI particle; RNA polymerase; インフルエンザウイルスA; RNAの転写の複製; インフルエンザウイルスA型; RNAの転写,複製; RNAポリメラーゼ遺伝子

The genome RNA segment 8 of influenza A virus encodes two nonstructural proteins, NS1 and NS2. Function of these proteins, in particular for NS2 protein, in viral replication cycle is unknown. We have succeeded to isolate an NS2 mutant. Wa-182, which produced a large amount of defective interfering(DI) particles lacking the PA polymerase gene. In the present study using the NS2 mutant Wa-182 and wild type viruses whose NS2 protein was expressed either at the beginning of infection or at the late phase of infection, we demonstrated (1) that NS2 protein promoted normal replication of genome RNA segments through the suppression of DI-RNA synthesis, (2) that NS2 protein conferred selective packaging of genome RNAs by an intermolecular recognition among RNA segments, and (3) that NS2 protein controlled the initiation of genome RNA replication by the regulation of cRNA synthesis. These observations indicate that the NS2 protein functions to be a regulator in multiple steps of viral growth cycle.

甲型流感病毒基因组RNA片段8编码两种非结构蛋白NS1和NS2。这些蛋白，特别是NS2蛋白在病毒复制周期中的功能尚不清楚。我们已成功分离到一个NS2突变体。产生大量缺乏PA聚合酶基因的缺陷干扰(DI)颗粒。在本研究中，我们利用NS2突变体WA-182和NS2蛋白在感染开始或感染后期表达的野生型病毒，证明了(1)NS2蛋白通过抑制DI-RNA合成促进了基因组RNA片段的正常复制，(2)NS2蛋白通过RNA片段之间的分子间识别实现了对基因组RNA的选择性包装，(3)NS2蛋白通过调节CRNA合成控制了基因组RNA复制的启动。这些观察表明，NS2蛋白在病毒生长周期的多个步骤中发挥调节作用。

项目成果

Masashi Urabe: "Persistence of viral genes in a variant of MDCK cells after productive replication of a mutant of influenza virus A/WSN." Arch.Virol.128. 97-110 (1993)

Masashi Urabe：“在 A/WSN 流感病毒突变体有效复制后，MDCK 细胞变体中病毒基因的持久性。”

Takato Odagiri: "Reversed misreading of a GC doublet by the modified T7 DNA polymerase, Sequenase." Virus Genes. in press.

Takato Odagiri：“通过修饰的 T7 DNA 聚合酶、测序酶逆转了 GC 双联体的误读。”

Takato Odagiri: "Structure and function of the influenza virus genome." Protein,Nuleic Acid,Enzyme. 37. 96-102 (1992)

Takato Odagiri：“流感病毒基因组的结构和功能。”

Takato Odagiri: "An amino acid change in the NS2 protein of influenza A virus mutant causes generation of defective interfering(DI) particles by amplirying DI RNAs and" J.Gen.Virol.75. 43-53 (1994)

Takato Odagiri：“甲型流感病毒突变体 NS2 蛋白中的氨基酸变化导致通过扩增 DI RNA 产生有缺陷的干扰 (DI) 颗粒”，J.Gen.Virol.75。

Takato Odagiri: "Synthesis of the NS2 nonstructural protein messenger RNA of intluenza A viruses occurs in the absence of viral proteinsynthesis." Arch.Virol.120. 281-228 (1991)

Takato Odagiri：“甲型流感病毒 NS2 非结构蛋白信使 RNA 的合成是在没有病毒蛋白合成的情况下进行的。”