Analysis of the role of autophagy in replication of herpes simplex virus in cell culture
Analysis of the role of autophagy in replication of herpes simplex virus in cell culture
复制标题
DOI：
10.1128/jvi.01356-07
复制
发表时间：
2007-11-01
影响因子：
5.4
通讯作者：
Leib, David A.
中科院分区：
文献类型：
--
作者：
Alexander, Diane E.;Ward, Stephen L.;Leib, David A.
编码ICP34.5的单纯疱疹病毒I型（HSV-1）神经病毒基因控制自噬途径。缺乏ICP 34.5的HSV-1毒株在动物模型和原代培养细胞中的生长和致病性减弱。虽然这种生长缺陷已被归因于ICP34.5无效病毒无法通过PKR抗病毒途径抵消翻译停滞的诱导，但自噬在HSV-1复制调节中的作用尚不清楚。在这里，我们表明，HSV-1感染诱导原代小鼠胚胎成纤维细胞的自噬和自噬体的形成增加到更大的程度与ICP34.5缺陷型病毒感染后。自噬途径的消除没有显著改变野生型HSV-1或ICP34.5突变体的复制。在HSV-1感染的细胞中，eIF 2 α的磷酸化状态和病毒蛋白积累没有变化，无法进行自噬。这些数据表明，虽然ICP34.5调节自噬，但ICP34.5对翻译停滞的预防而不是其对自噬的控制是原代细胞培养物中有效HSV-1复制的关键决定因素。
The herpes simplex virus type I (HSV-1) neurovirullence gene encoding ICP34.5 controls the autophagy pathway. HSV-1 strains lacking ICP34.5 are attenuated in growth and pathogenesis in animal models and in primary cultured cells. While this growth defect has been attributed to the inability of an ICP34.5-null virus to counteract the induction of translational arrest through the PKR antiviral pathway, the role of autophagy in the regulation of HSV-1 replication is unknown. Here we show that HSV-1 infection induces autophagy in primary murine embryonic fibroblasts and that autophagosorne formation is increased to a greater extent following infection with an ICP34.5-deficient virus. Elimination of the autophagic pathway did not significantly alter the replication of wild-type HSV-1 or ICP34.5 mutants. The phosphorylation state of eIF2 alpha and viral protein accumulation were unchanged in HSV-1-infected cells unable to undergo autophagy. These data show that while ICP34.5 regulates autophagy, it is the prevention of translational arrest by ICP34.5 rather than its control of autophagy that is the pivotal determinant of efficient HSV-1 replication in primary cell culture.