The eIF2α kinases inhibit vesicular stomatitis virus replication independently of eIF2α phosphorylation
The eIF2α kinases inhibit vesicular stomatitis virus replication independently of eIF2α phosphorylation
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DOI：
10.4161/cc.6323
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发表时间：
2008-08-01
期刊：
影响因子：
4.3
通讯作者：
Koromilas, Antonis E.
中科院分区：
文献类型：
--
作者：
Krishnamoorthy, Jothilatha;Mounir, Zineb;Koromilas, Antonis E.
eIF2 α 激酶参与了水泡性口炎病毒复制的抑制，但每种激酶对此过程的贡献尚未得到充分研究。使用来自敲除小鼠的小鼠胚胎成纤维细胞 (MEF)，我们发现 PKR 和 HRI 对 VSV 复制没有影响，而 PERK 和 GCN2 表现出很强的抑制作用。当使用含有 eIF2 α 丝氨酸 51 至丙氨酸突变的 MEF 时，我们发现 VSV 复制独立于 eIF2 α 磷酸化。然而，eIF2 α 激酶的激酶结构域对于抑制培养细胞中的 VSV 复制来说是必要且充分的。 eIF2 α 激酶激活诱导 PI3K-Akt/PKB 通路在抑制 VSV 复制中不起作用。我们的数据提供了强有力的证据，表明 VSV 复制不受 eIF2 α 磷酸化或下游效应通路（例如 PI3K-Akt/PKB 通路）的影响。因此，eIF2α激酶的抗病毒特性并不总是像之前认为的那样与其对宿主蛋白质合成的抑制作用有关，并且可能是由除eIF2α之外的蛋白质的磷酸化介导的。
The eIF2 alpha kinases have been involved in the inhibition of vesicular stomatatis virus replication but the contribution of each kinase to this process has not been fully investigated. Using mouse embryonic fibroblasts (MEFs) from knock-out mice we show that PKR and HRI have no effects on VSV replication as opposed to PERK and GCN2, which exhibit strong inhibitory effects. When MEFs containing the serine 51 to alanine mutation of eIF2 alpha were used, we found that VSV replication is independent of eIF2 alpha phosphorylation. Nevertheless, the kinase domain of the eIF2 alpha kinases is both necessary and sufficient to inhibit VSV replication in cultured cells. Induction of PI3K-Akt/PKB pathway by eIF2 alpha kinase activation plays no role in the inhibition of VSV replication. Our data provide strong evidence that VSV replication is not affected by eIF2 alpha phosphorylation or downstream effector pathways such as the PI3K-Akt/PKB pathway. Thus, the anti-viral properties of eIF2 alpha kinases are not always related to their inhibitory effects on host protein synthesis as previously thought and are possibly mediated by phosphorylation of proteins other than eIF2 alpha.