Garcin D, Latorre P, Kolakofsky D
Department of Genetics and Microbiology, University of Geneva School of Medicine, CMU, CH1211 Geneva, Switzerland.
J Virol. 1999 Aug;73(8):6559-65. doi: 10.1128/JVI.73.8.6559-6565.1999.
We have studied the relationship between the Sendai virus (SeV) C proteins (a nested set of four proteins initiated at different start codons) and the interferon (IFN)-mediated antiviral response in IFN-competent cells in culture. SeV strains containing wild-type or various mutant C proteins were examined for their ability (i) to induce an antiviral state (i.e., to prevent the growth of vesicular stomatitis virus [VSV] following a period of SeV infection), (ii) to induce the elevation of Stat1 protein levels, and (iii) to prevent IFN added concomitant with the SeV infection from inducing an antiviral state. We find that expression of the wild-type C gene and, specifically, the AUG114-initiated C protein prevents the establishment of an antiviral state: i.e., cells infected with wild-type SeV exhibited little or no increase in Stat1 levels and were permissive for VSV replication, even in the presence of exogenous IFN. In contrast, in cells infected with SeV lacking the AUG114-initiated C protein or containing a single amino acid substitution in the C protein, the level of Stat1 increased and VSV replication was inhibited. The prevention of the cellular IFN-mediated antiviral response appears to be a key determinant of SeV pathogenicity.
我们研究了仙台病毒（SeV）C蛋白（一组由不同起始密码子起始的四种嵌套蛋白）与培养的具有干扰素（IFN）活性的细胞中IFN介导的抗病毒反应之间的关系。检测了含有野生型或各种突变型C蛋白的SeV毒株的以下能力：（i）诱导抗病毒状态（即，在SeV感染一段时间后阻止水疱性口炎病毒[VSV]生长）；（ii）诱导Stat1蛋白水平升高；（iii）阻止与SeV感染同时添加的IFN诱导抗病毒状态。我们发现野生型C基因的表达，特别是由AUG114起始的C蛋白的表达可阻止抗病毒状态的建立：即，感染野生型SeV的细胞Stat1水平几乎没有增加或没有增加，并且即使存在外源性IFN也允许VSV复制。相反，在感染缺乏由AUG114起始的C蛋白的SeV或C蛋白中含有单个氨基酸取代的SeV的细胞中，Stat1水平升高且VSV复制受到抑制。细胞IFN介导的抗病毒反应的抑制似乎是SeV致病性的关键决定因素。
