Regulation of paramyxovirus gene expression and pathogenesis by host factors.

宿主因素对副粘病毒基因表达和发病机制的调节。

• 批准号: 12470071
• 负责人: YOSHIDA Tetsuya
• 金额: $ 3.46万
• 依托单位: Hiroshima University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-12470071/
• 关键词: paramyxovirus; Sendai virus; pathogenicity; gene expression; V protein; innate immunity; leader sequence; host factors; 弱毒性; リバースジェネティクス; 浜松株; 弱毒化; リーダー変異; ウイルス回収系; V蛋白; ゲノム複製; 塩基配列; ウイルス回收系; Zn結合能

Sendai virus (SeV) is a paramyxovirus causing bronchopneumonitis in rodents and possesses a nonsegmented single-stranded minus-sense RNA as a genome. In the present study we examined the function of SeV accessory V protein and the attenuation of SeV pathogenicity by egg passages to study the regulation of SeV gene expression and pathogenesis by host factors, and the following results were obtained.(1) The V protein of the Hamamatsu strain, a highly virulent field SeV isolate, has been shown to have a luxury function to facilitate virus propagation in mice but not in cultured cells as well as that of the Z strain, an egg-adapted avirulent laboratory SeV strain, and to be prominent only if virus replication was restricted. (ref. 4, 8, 14, and 17)(2) The luxuary function of the V protein has been shown to be dependent on the amino acid residues at the C terminus of the protein, which are highly conserved among paramyxoviruses, probably via protein conformation dependent on Zn binding. (ref. 1, 4, 8, and 13)(3) The V protein function, probably by coping with the host innate immunity, antagonized neither interferon action nor NK cell activity. The cellular target of the V protein remains to be clarified. (ref. 17, unpublished data)(4) Attenuation of SeV pathogenicity by egg passages has been shown to be caused at least by mutations of the nucleotides at position 20 and 24 in the leader sequence, suggesting that the leader mutaions affect virus pathogenesis by altering virus replication via interaction with host factors. (ref. 6, 12, and 14)

仙台病毒（SeV）是一种引起啮齿动物支气管炎的副粘病毒，基因组为非节段单链负义RNA。本研究通过检测SeV辅助V蛋白的功能和SeV卵传代对SeV致病性的减弱作用，探讨宿主因子对SeV基因表达和致病性的调控，获得以下结果。(1)已经显示，高毒力的SeV野毒株Hamamatsu株的V蛋白具有促进病毒在小鼠中繁殖的奢侈功能，但在培养细胞中不具有这种功能，以及Z株的V蛋白，该Z株是一种蛋适应的无毒力的实验室SeV株，并且仅在病毒复制受到限制时才突出。(ref. 4、8、14和17）（2）V蛋白的luxuary功能已被证明依赖于蛋白C末端的氨基酸残基，这些残基在副粘病毒中高度保守，可能是通过依赖于锌结合的蛋白质构象。(ref.（3）V蛋白的功能，可能是通过应对宿主的先天免疫，既不拮抗干扰素的作用，也不拮抗NK细胞的活性。V蛋白的细胞靶点仍有待澄清。(ref.（4）通过卵传代的SeV致病性的减弱已经显示至少由前导序列中的位置20和24处的核苷酸的突变引起，这表明前导突变通过与宿主因子相互作用改变病毒复制来影响病毒发病机制。(ref.（第6、12和14段）

项目成果

Sakaguchi, T.: "Alteration of Sendai virus morphogenesis and nucleocapsid incorporation by the mutation of cysteine residues of the matrix protein."Journal of Virology. 76. 1682-1690 (2002)

Sakaguchi, T.：“通过基质蛋白半胱氨酸残基的突变改变仙台病毒形态发生和核衣壳掺入。”病毒学杂志。

Fujii, Y.: "Involvement of the leader sequence in Sendai virus pathogenesis revealed by recovery of a pathogenic field isolate from cDNA."Journal of Virology. 76. 8540-8547 (2002)

Fujii, Y.：“通过从 cDNA 中分离出致病区域，揭示了仙台病毒发病机制中前导序列的参与。”病毒学杂志。

Takemasa Sakaguchi: "Masking of the contribution of V protein to Sendai virus pathogenesis in an infection model with a highly virulent field isolate"Virology. 313. 581-587 (2003)

Takemasa Sakaguchi：“在高毒力野外分离株的感染模型中掩盖 V 蛋白对仙台病毒发病机制的贡献”病毒学。

Huang, C.: "Involvement of the zinc-binding capacity of Sendai virus V protein in viral pathogenesis."Journal of Virology. 74. 7834-7841 (2000)

Huang, C.：“仙台病毒 V 蛋白的锌结合能力在病毒发病机制中的参与。”病毒学杂志。

Fan, X.-H.: "Emergence of anti-inflammatory monocytes in long-term surviving host of IL-10-transduced liver allografts."Cytokine. 13. 183-187 (2001)

Fan, X.-H.：“IL-10 转导的同种异体肝移植物长期存活宿主中抗炎单核细胞的出现。”细胞因子。