Host translation shutoff mediated by non-structural protein 2 is a critical factor in the antiviral state resistance of Venezuelan equine encephalitis virus
Host translation shutoff mediated by non-structural protein 2 is a critical factor in the antiviral state resistance of Venezuelan equine encephalitis virus
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DOI：
10.1016/j.virol.2016.06.005
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发表时间：
2016-09-01
期刊：
影响因子：
3.7
通讯作者：
Klimstra, William B.
中科院分区：
文献类型：
--
作者：
Bhalla, Nishank;Sun, Chengqun;Klimstra, William B.
先前大多数关于α病毒对干扰素- α / β (ifn - α / β)反应拮抗的研究都集中在干扰素- α / β诱导和/或受体信号级联的中断上。感染委内瑞拉马脑炎α病毒（VEEV）或辛德比斯病毒（SINV）的小鼠可诱导血清ifn - α / β，从而在未感染的细胞中诱导系统抗病毒状态，成功地控制了SINV，但不控制VEEV的复制。此外，在体外，VEEV的复制比SINV更能抵抗预先存在的抗病毒状态。虽然宿主大分子关闭被认为是ifn - α / β诱导的主要拮抗剂，但甲病毒对预先存在的抗病毒状态产生耐药性的潜在机制尚未完全确定，VEEV产生更大耐药性的机制也尚未完全确定。在这里，我们分离了多个甲型病毒的病毒转录和翻译关闭，鉴定了诱导每种活性的病毒蛋白，并证明了VEEV非结构蛋白2诱导的翻译关闭可能是增强该甲型病毒抗病毒状态抗性的关键因素。(C) 2016 Elsevier Inc.版权所有。
Most previous studies of interferon-alpha/beta (IFN-alpha/beta) response antagonism by alphaviruses have focused upon interruption of IFN-alpha/beta induction and/or receptor signaling cascades. Infection of mice with Venezuelan equine encephalitis alphavirus (VEEV) or Sindbis virus (SINV) induces serum IFN-alpha/beta, that elicits a systemic antiviral state in uninfected cells successfully controlling SINV but not VEEV replication. Furthermore, VEEV replication is more resistant than that of SINV to a pre-existing antiviral state in vitro. While host macromolecular shutoff is proposed as a major antagonist of IFN-alpha/beta induction, the underlying mechanisms of alphavirus resistance to a pre-existing antiviral state are not fully defined, nor is the mechanism for the greater resistance of VEEV. Here, we have separated viral transcription and translation shutoff with multiple alphaviruses, identified the viral proteins that induce each activity, and demonstrated that VEEV nonstructural protein 2-induced translation shutoff is likely a critical factor in enhanced antiviral state resistance of this alphavirus. (C) 2016 Elsevier Inc. All rights reserved.