Binding of the pathogen receptor HSP90AA1 to avibirnavirus VP2 induces autophagy by inactivating the AKT-MTOR pathway.
Binding of the pathogen receptor HSP90AA1 to avibirnavirus VP2 induces autophagy by inactivating the AKT-MTOR pathway.
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DOI：
10.1080/15548627.2015.1017184
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发表时间：
2015
期刊：
影响因子：
13.3
通讯作者：
Zhou J
中科院分区：
文献类型：
--
作者：
Hu B;Zhang Y;Jia L;Wu H;Fan C;Sun Y;Ye C;Liao M;Zhou J
自噬是宿主先天免疫和适应性免疫的重要组成部分。病毒已经发展出多种策略来逃避或利用自噬来生存。自噬途径对病毒入侵的反应文献很少。在这里，我们报道了病原体受体HSP90AA1（热休克蛋白90 kDa α[细胞质]，A类成员1）通过AKT-MTOR（雷帕霉素的机制靶点）依赖途径诱导自噬。透射电镜和共聚焦显微镜显示细胞内的自溶酶体包装了鸟比病毒颗粒。自噬检测显示，早期鸟比病毒感染不仅使轻链3 (LC3)-II的数量增加，而且使AKT-MTOR去磷酸化水平上调。通过RNA干扰敲低hsp90a1 - akt - mtor可抑制鸟比病毒感染过程中的自噬。病毒滴度测定进一步证实，自噬抑制而非诱导增强了鸟比病毒的复制。随后，我们发现HSP90AA1与病毒蛋白VP2结合导致自噬诱导和AKT-MTOR通路失活。总之，我们的研究结果表明，在早期感染中，细胞表面蛋白HSP90AA1（一种鸟比病毒结合受体）通过HSP90AA1- akt - mtor途径诱导自噬。我们发现，在病毒识别后，HSP90AA1和AKT-MTOR通路之间的直接联系触发自噬，这是控制感染的关键步骤。
Autophagy is an essential component of host innate and adaptive immunity. Viruses have developed diverse strategies for evading or utilizing autophagy for survival. The response of the autophagy pathways to virus invasion is poorly documented. Here, we report on the induction of autophagy initiated by the pathogen receptor HSP90AA1 (heat shock protein 90 kDa α [cytosolic], class A member 1) via the AKT-MTOR (mechanistic target of rapamycin)-dependent pathway. Transmission electron microscopy and confocal microscopy revealed that intracellular autolysosomes packaged avibirnavirus particles. Autophagy detection showed that early avibirnavirus infection not only increased the amount of light chain 3 (LC3)-II, but also upregulated AKT-MTOR dephosphorylation. HSP90AA1-AKT-MTOR knockdown by RNA interference resulted in inhibition of autophagy during avibirnavirus infection. Virus titer assays further verified that autophagy inhibition, but not induction, enhanced avibirnavirus replication. Subsequently, we found that HSP90AA1 binding to the viral protein VP2 resulted in induction of autophagy and AKT-MTOR pathway inactivation. Collectively, our findings suggest that the cell surface protein HSP90AA1, an avibirnavirus-binding receptor, induces autophagy through the HSP90AA1-AKT-MTOR pathway in early infection. We reveal that upon viral recognition, a direct connection between HSP90AA1 and the AKT-MTOR pathway trigger autophagy, a critical step for controlling infection.