Ouwendijk Werner J D, van Veen Suzanne, Mahalingam Ravi, Verjans Georges M G M
Department of Viroscience, Erasmus MC, Rotterdam, The Netherlands.
Department of Neurology, University of Colorado School of Medicine, Aurora, Colorado, USA.
J Gen Virol. 2017 Oct;98(10):2582-2588. doi: 10.1099/jgv.0.000925.
The alphaherpesvirus simian varicella virus (SVV) causes varicella and zoster in nonhuman primates. Herpesviruses evolved elaborate mechanisms to escape host immunity, but the immune evasion strategies employed by SVV remain ill-defined. We analysed whether SVV impairs the cellular response to key antiviral cytokine interferon-γ (IFNγ). SVV infection inhibited the expression of IFNγ-induced genes like C-X-C motif chemokine 10 and interferon regulatory factor 1. Phosphorylation and nuclear translocation of the signal transducer and activator of transcription 1 (STAT1) was blocked in SVV-infected cells, which did not involve cellular and viral phosphatases. SVV infection did not downregulate IFNγ receptor α and β chain expression on the cell surface. Instead, STAT1, Janus tyrosine kinases 1 (JAK1) and JAK2 protein levels were significantly decreased in SVV-infected cells. Collectively, these results demonstrate that SVV targets three proteins in the IFNγ signal transduction pathway to escape the antiviral effects of IFNγ.
甲型疱疹病毒猴水痘病毒（SVV）可在非人灵长类动物中引起水痘和带状疱疹。疱疹病毒进化出了复杂的机制来逃避宿主免疫，但SVV所采用的免疫逃逸策略仍不清楚。我们分析了SVV是否会损害细胞对关键抗病毒细胞因子干扰素-γ（IFNγ）的反应。SVV感染抑制了IFNγ诱导基因如C-X-C基序趋化因子10和干扰素调节因子1的表达。在SVV感染的细胞中，信号转导子和转录激活子1（STAT1）的磷酸化和核转位被阻断，这与细胞和病毒磷酸酶无关。SVV感染并未下调细胞表面IFNγ受体α和β链的表达。相反，在SVV感染的细胞中，STAT1、Janus酪氨酸激酶1（JAK1）和JAK2的蛋白水平显著降低。总体而言，这些结果表明SVV靶向IFNγ信号转导途径中的三种蛋白质以逃避IFNγ的抗病毒作用。
