Autophagy Negatively Regulates Transmissible Gastroenteritis Virus Replication.
Autophagy Negatively Regulates Transmissible Gastroenteritis Virus Replication.
复制标题
自噬负向调节传染性胃肠炎病毒复制
DOI：
10.1038/srep23864
复制
发表时间：
2016-03-31
影响因子：
4.6
通讯作者：
Wang Y
中科院分区：
文献类型：
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作者：
Guo L;Yu H;Gu W;Luo X;Li R;Zhang J;Xu Y;Yang L;Shen N;Feng L;Wang Y
自噬是一种进化上古老的途径，已被证明是重要的先天免疫防御几种病毒。然而，关于自噬在传染性胃肠炎病毒（TGEV）复制中的调节作用知之甚少。在这项研究中，我们发现TGEV感染增加了宿主细胞胞质中自噬体样双膜和单膜囊泡的数量，这是一种已知与自噬相关的现象。此外，自噬体标记蛋白LC 3-II的量增加需要病毒复制。TGEV感染的细胞发生自噬流，表明TGEV感染引发了完整的自噬反应。当自噬被wortmannin或LY 294002抑制时，TGEV复制增加。通过使用siRNA双链体进一步证实了通过自噬抑制的病毒产量增加，通过siRNA双链体，自噬所需的三种蛋白质被耗尽。此外，当雷帕霉素激活自噬时，TGEV复制受到抑制。自噬的抗病毒应答通过使用siRNA降低基因p300的表达来证实，否则基因p300抑制自噬。总之，结果表明TGEV感染激活自噬，然后自噬抑制TGEV进一步复制。
Autophagy is an evolutionarily ancient pathway that has been shown to be important in the innate immune defense against several viruses. However, little is known about the regulatory role of autophagy in transmissible gastroenteritis virus (TGEV) replication. In this study, we found that TGEV infection increased the number of autophagosome-like double- and single-membrane vesicles in the cytoplasm of host cells, a phenomenon that is known to be related to autophagy. In addition, virus replication was required for the increased amount of the autophagosome marker protein LC3-II. Autophagic flux occurred in TGEV-infected cells, suggesting that TGEV infection triggered a complete autophagic response. When autophagy was pharmacologically inhibited by wortmannin or LY294002, TGEV replication increased. The increase in virus yield via autophagy inhibition was further confirmed by the use of siRNA duplexes, through which three proteins required for autophagy were depleted. Furthermore, TGEV replication was inhibited when autophagy was activated by rapamycin. The antiviral response of autophagy was confirmed by using siRNA to reduce the expression of gene p300, which otherwise inhibits autophagy. Together, the results indicate that TGEV infection activates autophagy and that autophagy then inhibits further TGEV replication.