Zika virus inhibits type-I interferon production and downstream signaling
Zika virus inhibits type-I interferon production and downstream signaling
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DOI：
10.15252/embr.201642627
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发表时间：
2016-12-01
期刊：
影响因子：
7.7
通讯作者：
Hobman, Tom C.
中科院分区：
文献类型：
--
作者：
Kumar, Anil;Hou, Shangmei;Hobman, Tom C.
寨卡病毒是一种新兴的蚊媒病原体，与成人的格林-巴利综合征和新生儿的小头畸形和其他神经缺陷有关。尽管世界卫生组织宣布该病毒进入国际紧急状态，但人们对其生物学知之甚少。在这里，我们调查的策略所采用的病毒抑制宿主的抗病毒反应。我们观察到，一旦建立，寨卡病毒感染是不受干扰素治疗的，这表明该病毒对宿主细胞防御采取了有效的对策。实验证实了这一点，表明寨卡病毒感染损害了I型干扰素的诱导以及下游干扰素刺激基因。多种病毒蛋白影响这些过程。病毒介导的STAT 2降解可减少I型和III型干扰素介导的信号传导。此外，寨卡病毒的NS 5与STAT 2结合，其表达与蛋白酶体降解STAT 2相关。总之，我们的发现为寨卡病毒如何阻止细胞防御系统提供了关键见解。这反过来对理解发病机制很重要，并可能有助于设计抗病毒疗法。
Zika virus is an emerging mosquito-borne pathogen that is associated with Guillain-Barre syndrome in adults and microcephaly and other neurological defects in newborns. Despite being declared an international emergency by the World Health Organization, comparatively little is known about its biology. Here, we investigate the strategies employed by the virus to suppress the host antiviral response. We observe that once established, Zika virus infection is impervious to interferon treatment suggesting that the virus deploys effective countermeasures to host cell defences. This is confirmed by experiments showing that Zika virus infection impairs the induction of type-I interferon as well as downstream interferon-stimulated genes. Multiple viral proteins affect these processes. Virus-mediated degradation of STAT2 acts to reduce type-I and type-III interferon-mediated signaling. Further, the NS5 of Zika virus binds to STAT2, and its expression is correlated with STAT2 degradation by the proteasome. Together, our findings provide key insights into how Zika virus blocks cellular defense systems. This in turn is important for understanding pathogenesis and may aid in designing antiviral therapies.