Xenophagy in herpes simplex virus replication and pathogenesis
Xenophagy in herpes simplex virus replication and pathogenesis
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DOI：
10.4161/auto.5222
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发表时间：
2008-01-01
期刊：
影响因子：
13.3
通讯作者：
Leib, David A.
中科院分区：
文献类型：
--
作者：
Alexander, Diane E.;Leib, David A.
自噬在一定程度上是宿主吞噬和降解细胞内病原体的重要防御机制，这一过程被称为异种吞噬。自噬在复制和发病机制方面对入侵微生物是有害的，许多病原体要么抑制自噬反应，要么利用这一途径来延长其生命周期。单纯疱疹病毒1型（HSV-1）通过其神经毒力蛋白ICP34.5抵消异种吞噬的诱导。ICP34.5结合蛋白磷酸酶W来对抗pkr介导的eIF2 α磷酸化，并结合自噬促进蛋白Beclin 1。通过这些相互作用，ICP34.5阻止翻译阻滞并下调自噬体的形成。而自噬拮抗促进神经毒力，它没有影响复制HSV-1在允许培养细胞。正如本文所讨论的，这项工作提出了一些问题，如icp34.5介导的自噬抑制机制，以及自噬拮抗在HSV-1生命周期中的作用。
Autophagy functions in part as an important host defense mechanism to engulf and degrade intracellular pathogens, a process that has been termed xenophagy. Xenophagy is detrimental to the invading microbe in terms of replication and pathogenesis and many pathogens either dampen the autophagic response, or utilize the pathway to enhance their life cycle. Herpes simplex virus type 1 (HSV-1) counteracts the induction of xenophagy through its neurovirulence protein, ICP34.5. ICP34.5 binds protein phosphatase W to counter PKR-mediated phosphorylation of eIF2 alpha, and also binds the autophagy-promoting protein Beclin 1. Through these interactions, ICP34.5 prevents translational arrest and downregulates the formation of autophagosomes. Whereas autophagy antagonism promotes neurovirulence, it has no impact on the replication of HSV-1 in permissive cultured cells. As discussed in this article, this work raises a number of questions as to the mechanism of ICP34.5-mediated inhibition of autophagy, as well as to the role of autophagy antagonism in the lifecycle of HSV-1.