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草鱼呼肠孤病毒通过 Akt/mTOR 通路触发自噬从而增强病毒复制。

Grass Carp Reovirus triggers autophagy enhancing virus replication via the Akt/mTOR pathway.

机构信息

School of Biology & Basic Medical Science, Soochow University, Suzhou, 215123, China; Agricultural Biotechnology Research Institute, Agricultural Biotechnology and Ecological Research Institute, Soochow University, Suzhou, 215123, China.

School of Biology & Basic Medical Science, Soochow University, Suzhou, 215123, China.

出版信息

Fish Shellfish Immunol. 2022 Sep;128:148-156. doi: 10.1016/j.fsi.2022.07.069. Epub 2022 Jul 31.

Abstract

Autophagy impacts the replication cycle of many viruses. Grass Carp Reovirus (GCRV) is an agent that seriously affects the development of the grass carp aquaculture industry. The role of autophagy in GCRV infection is not clearly understood. In this study, we identified that GCRV infection triggered autophagy in CIK cells, which was demonstrated by transmission electron microscopy, the conversion of LC3B I to LC3B II and the level of autophagy substrate p62. Furthermore, we found that GCRV infection activated Akt-mTOR signaling pathway, and the conversion of LC3B I to LC3B II was increased by inhibiting mTOR with rapamycin (Rap) but decreased by activating Akt with insulin. We then assessed the effects of autophagy on GCRV replication. We found that inducing autophagy with Rap promoted GCRV proliferation but inhibiting autophagy with 3 MA or CQ inhibited GCRV replication in CIK cells. Moreover, it was found that enhancing Akt-mTOR activity by insulin, GCRV VP7 protein and viral titers of GCRV were decreased. Collectively, these results indicated that GCRV infection induced autophagy involved in GCRV replication via the Akt-mTOR signal pathway. Thus, new insights into GCRV pathogenesis and antiviral treatment strategies are provided.

摘要

自噬影响许多病毒的复制周期。草鱼呼肠孤病毒(GCRV)是一种严重影响草鱼养殖业发展的病原体。自噬在 GCRV 感染中的作用尚不清楚。在本研究中,我们发现 GCRV 感染在 CIK 细胞中触发了自噬,这可以通过透射电子显微镜、LC3B I 向 LC3B II 的转化以及自噬底物 p62 的水平来证明。此外,我们发现 GCRV 感染激活了 Akt-mTOR 信号通路,并且用雷帕霉素(Rap)抑制 mTOR 会增加 LC3B I 向 LC3B II 的转化,而用胰岛素激活 Akt 则会降低 LC3B I 向 LC3B II 的转化。然后,我们评估了自噬对 GCRV 复制的影响。我们发现,用 Rap 诱导自噬会促进 GCRV 的增殖,但用 3-MA 或 CQ 抑制自噬会抑制 CIK 细胞中的 GCRV 复制。此外,还发现胰岛素、GCRV VP7 蛋白和 GCRV 的病毒滴度增强 Akt-mTOR 活性会降低。综上所述,这些结果表明,GCRV 感染诱导的自噬通过 Akt-mTOR 信号通路参与了 GCRV 的复制。因此,为 GCRV 的发病机制和抗病毒治疗策略提供了新的见解。

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