Rinderpest virus blocks type I and type II interferon action: Role of structural and nonstructural proteins
Rinderpest virus blocks type I and type II interferon action: Role of structural and nonstructural proteins
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DOI：
10.1128/jvi.02720-05
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发表时间：
2006-08-01
影响因子：
5.4
通讯作者：
Baron, Michael D.
中科院分区：
文献类型：
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作者：
Nanda, Sambit K.;Baron, Michael D.
牛瘟病毒（Rinderpest virus，RPV）是一种与人类麻疹病毒密切相关的副粘病毒。它在牛、布法罗和一些野生动物中引起严重疾病;虽然它可以感染人类，但它不会引起疾病。在这里，我们表明，RPV块的行动，I型（α）和II型（γ）干扰素（IFN）通过阻断磷酸化和核转位的STAT1和STAT2，这种块是不相关的物种特异性。此外，野生型病毒和疫苗株阻断IFN的作用。与其他一些副粘病毒不同的是，STAT1和STAT2在病毒感染后都不会降解。STAT1被病毒结构蛋白P和非结构蛋白V结合，从而募集到细胞中病毒蛋白的浓度。虽然P和V蛋白都与STAT1结合，并且当在转染细胞中表达时可以阻断IFN作用，但是P蛋白的IFN拮抗剂活性比V蛋白弱。在转染实验中，病毒C蛋白似乎也微弱地阻断IFN诱导的STAT1活化。然而，敲除病毒的研究表明，病毒V蛋白似乎是在病毒感染的情况下IFN信号传导的主要抑制剂，因为病毒V表达的预防恢复了受感染细胞的IFN敏感性。尽管在病毒感染的细胞中观察到STAT2分布模式的变化，但STAT2不被任何病毒蛋白结合。
Rinderpest virus (RPV) is a paramyxovirus closely related to the human pathogen Measles virus. It causes severe disease in cattle, buffalo, and some wild animals; although it can infect humans, it does not cause disease. Here, we demonstrate that RPV blocks the action of both type I (alpha) and type II (gamma) interferons (IFNs) by blocking the phosphorylation and nuclear translocation of STAT1 and STAT2 and that this block is not related to species specificity. In addition, both wild-type virulent and vaccine strains of the virus blocked IFN action. Unlike the case with some other paramyxoviruses, neither STAT1 nor STAT2 is degraded upon virus infection. STAT1 is bound by both the viral structural protein P, and thereby recruited to concentrations of viral protein in the cell, and the nonstructural protein V. Although both P and V proteins bind to STAT1 and can block IFN action when expressed in transfected cells, the IFN antagonist activity of the P protein is weaker than that of the V protein. The viral C protein also seems to weakly block IFN-induced activation of STAT1 in transfection experiments. However, studies with knockout viruses showed that the viral V protein appears to be the dominant inhibitor of IFN signaling in the context of virus infection, since prevention of viral V expression restored the IFN sensitivity of infected cells. Although a change in the distribution pattern of STAT2 was observed in virus-infected cells, STAT2 was not bound by any viral protein.