Maintenance of endoplasmic reticulum (ER) homeostasis in herpes simplex virus type 1-infected cells through the association of a viral glycoprotein with PERK, a cellular ER stress sensor
Maintenance of endoplasmic reticulum (ER) homeostasis in herpes simplex virus type 1-infected cells through the association of a viral glycoprotein with PERK, a cellular ER stress sensor
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DOI：
10.1128/jvi.02191-06
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发表时间：
2007-04-01
影响因子：
5.4
通讯作者：
Mohr, Ian
中科院分区：
文献类型：
--
作者：
Mulvey, Matthew;Arias, Carolina;Mohr, Ian
在病毒努力支配和控制关键细胞途径的过程中，病毒在其宿主内产生相当大的细胞内应激。特别是，常驻内质网（ER）伴侣蛋白正确处理客户端蛋白负荷的急性增加的能力受到了极大的挑战。这种改变通常诱导未折叠的蛋白质反应，其中一个组分通过IRE 1发挥作用，通过扩大折叠能力恢复ER稳态，而另一个臂激活eIF-2 α（真核起始因子2的α亚基）激酶PERK，瞬时阻止新多肽客户的产生。然而，病毒，如单纯疱疹病毒1型（HSV-1），会竭尽全力阻止由eIF-2 α磷酸化引起的翻译抑制。在这里，我们建立PERK，而不是IRE 1，抵抗激活急性ER应激HSV-1感染的细胞。这需要PERK的ER管腔结构域，其与病毒糖蛋白gB相关。引人注目的是，gB以PERK依赖性方式调节病毒蛋白质积累。这是第一次描述病毒编码的PERK特异性效应子，并定义了病毒能够维持ER稳态的新策略。
In the efforts of viruses to dominate and control critical cellular pathways, viruses generate considerable intracellular stress within their hosts. In particular, the capacity of resident endoplasmic reticulum (ER) chaperones to properly process the acute increase in client protein load is significantly challenged. Such alterations typically induce the unfolded protein response, one component of which acts through IRE1 to restore ER homeostasis by expanding the folding capabilities, whereas the other arm activates the eIF-2 alpha (alpha subunit of eukaryotic initiation factor 2) kinase PERK to transiently arrest production of new polypeptide clientele. Viruses, such as herpes simplex virus type 1 (HSV-1), however, go to great lengths to prevent the inhibition of translation resulting from eIF-2 alpha phosphorylation. Here, we establish that PERK, but not IRE1, resists activation by acute ER stress in HSV-1-infected cells. This requires the ER luminal domain of PERK, which associates with the viral glycoprotein gB. Strikingly, gB regulates viral protein accumulation in a PERK-dependent manner. This is the first description of a virus-encoded PERK-specific effector and defines a new strategy by which viruses are able to maintain ER homeostasis.