Oncolytic vesicular stomatitis virus induces via signaling through PKR, Fas, and Daxx
Oncolytic vesicular stomatitis virus induces via signaling through PKR, Fas, and Daxx
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DOI：
10.1128/jvi.01760-06
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发表时间：
2007-03-01
影响因子：
5.4
通讯作者：
Lyles, Douglas S.
中科院分区：
文献类型：
--
作者：
Gaddy, Daniel F.;Lyles, Douglas S.
水疱性口炎病毒（VSV）基质(M)蛋白突变体是一种很有前途的癌症治疗溶瘤剂。先前的研究表明，Fas和PKR与其他病毒诱导的细胞凋亡有关。在这里，我们发现Fas和PKR的显性阴性突变体抑制M蛋白突变体病毒诱导的细胞凋亡。大多数先前的研究都集中在适配器蛋白FADD作为fas介导的细胞凋亡的必要换能器。而显性阴性FADD的表达对M蛋白突变体VSV诱导细胞凋亡的影响不大。相反，病毒诱导的细胞凋亡被适配器蛋白Daxx的显性阴性突变体的表达所抑制。这些数据表明，在M蛋白突变体VSV诱导的细胞凋亡中，Daxx比FADD更重要。这些结果表明，PKR-和fas介导的信号通路在M蛋白突变体VSV感染期间的细胞死亡中发挥重要作用，并且Daxx通过介导病毒诱导的细胞凋亡在宿主对病毒感染的应答中具有新的功能。
Matrix (M) protein mutants of vesicular stomatitis virus (VSV) are promising oncolytic agents for cancer therapy. Previous research has implicated Fas and PKR in apoptosis induced by other viruses. Here, we show that dominant-negative mutants of Fas and PKR inhibit M protein mutant virus-induced apoptosis. Most previous research has focused on the adapter protein FADD as a necessary transducer of Fas-mediated apoptosis. However, the expression of dominant-negative FADD had little effect on the induction of apoptosis by M protein mutant VSV. Instead, virus-induced apoptosis was inhibited by the expression of a dominant-negative mutant of the adapter protein Daxx. These data indicate that Daxx is more important than FADD for apoptosis induced by M protein mutant VSV. These results show that PKR- and Fas-mediated signaling play important roles in cell death during M protein mutant VSV infection and that Daxx has novel functions in the host response to virus infection by mediating virus-induced apoptosis.