Herpes Simplex Virus 2 Infection Impacts Stress Granule Accumulation
Herpes Simplex Virus 2 Infection Impacts Stress Granule Accumulation
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DOI：
10.1128/jvi.00313-12
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发表时间：
2012-08-01
影响因子：
5.4
通讯作者：
Banfield, Bruce W.
中科院分区：
文献类型：
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作者：
Finnen, Renee L.;Pangka, Kyle R.;Banfield, Bruce W.
干扰应激颗粒（SG）积累作为不同病毒促进其复制和科普翻译停滞的常用策略越来越受到重视。在这里，我们通过监测SG组分T细胞内部抗原1（TIA-1）、Ras-GT3激活SH 3结构域结合蛋白（G3 BP）和多聚腺苷酸结合蛋白（PABP）的定位，研究了单纯疱疹病毒2型（HSV-2）感染对SG积累的影响。我们的研究结果表明，SG不积累在HSV-2感染的细胞和HSV-2可以干扰砷诱导的SG积累感染后早期。令人惊讶的是，尽管真核生物翻译起始因子2 α（eIF 2 α）的磷酸化增加，但SG积累受到抑制，这意味着HSV-2编码先前未识别的旨在维持eIF 2 α下游翻译起始的活性。SG积累没有抑制HSV-2感染的细胞与pateamine A，诱导剂的工作独立于eIF 2 α磷酸化。在对感染的细胞进行苯丁胺A处理后积累的SG含有G3 BP和PABP，但基本上不含TIA-1。我们还鉴定了在感染后期形成的含有TIA-1的新型核结构。这些结构包含RNA结合蛋白68-kDa Src-有丝分裂相关（Sam 68），并且在用病毒DNA复制抑制剂处理的感染细胞中明显不存在，表明它们是病毒复制周期中晚期事件的结果。
Interference with stress granule (SG) accumulation is gaining increased appreciation as a common strategy used by diverse viruses to facilitate their replication and to cope with translational arrest. Here, we examined the impact of infection by herpes simplex virus 2 (HSV-2) on SG accumulation by monitoring the localization of the SG components T cell internal antigen 1 (TIA-1), Ras-GTPase-activating SH3-domain-binding protein (G3BP), and poly(A)-binding protein (PABP). Our results indicate that SGs do not accumulate in HSV-2-infected cells and that HSV-2 can interfere with arsenite-induced SG accumulation early after infection. Surprisingly, SG accumulation was inhibited despite increased phosphorylation of eukaryotic translation initiation factor 2 alpha (eIF2 alpha), implying that HSV-2 encodes previously unrecognized activities designed to maintain translation initiation downstream of eIF2 alpha. SG accumulation was not inhibited in HSV-2-infected cells treated with pateamine A, an inducer that works independently of eIF2 alpha phosphorylation. The SGs that accumulated following pateamine A treatment of infected cells contained G3BP and PABP but were largely devoid of TIA-1. We also identified novel nuclear structures containing TIA-1 that form late in infection. These structures contain the RNA binding protein 68-kDa Src-associated in mitosis (Sam68) and were noticeably absent in infected cells treated with inhibitors of viral DNA replication, suggesting that they arise as a result of late events in the virus replicative cycle.