TCP1 mediates gp37 of avian leukosis virus subgroup J to inhibit autophagy through activating AKT in DF-1 cells
TCP1 mediates gp37 of avian leukosis virus subgroup J to inhibit autophagy through activating AKT in DF-1 cells
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TCP1介导禽白血病病毒J亚型gp37通过激活DF-1细胞中的AKT抑制自噬
DOI：
10.1016/j.vetmic.2022.109472
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发表时间：
2022
期刊：
影响因子：
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通讯作者：
Qingmei Xie
中科院分区：
文献类型：
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作者：
Xinheng Zhang;Liyi Chen;Zhihong Liao;Zhenkai Dai;Yiming Yan;Ziqi Yao;Sheng Chen;Zi Xie;Qiqi Zhao;Feng Chen;Qingmei Xie
自噬是一个保守的过程，细胞通过它来维持内稳态。然而，自噬的异常可能导致包括癌症在内的各种疾病的发展。J亚群禽白血病病毒(ALV-J)是一种致癌的外源性逆转录病毒，在易感宿主体内可引起严重的免疫抑制和肿瘤的发生。这项研究首次揭示了ALV-J通过包膜蛋白gp37抑制自噬。在这里，我们证明了包膜蛋白gp37阻止了自噬小体与溶酶体的融合，并诱导了不完全自噬。有趣的是，其他实验表明，宿主伴侣蛋白TCP1也是自噬抑制因子，并阻断DF-1细胞的自噬流动过程。通过免疫沉淀实验，我们发现TCP1与gp37相互作用。此外，TCP1基因敲除也取消了gp37介导的对DF-1细胞自噬的抑制。此外，TCP1通过激活AKT促进病毒在DF-1细胞中的复制，从而介导ALV-J的gp37抑制自噬。·ALV-J通过包膜蛋白gp37抑制DF-1细胞的自噬。·gp37阻断自噬小体与溶酶体的融合，诱导DF-1细胞不完全自噬。·TCP1通过激活AKT促进病毒在DF-1细胞中的复制，介导ALV-J的gp37抑制自噬。
Autophagy is a conserved process by which cells maintain homeostasis. However, abnormalities in autophagy can lead to the development of various diseases, including cancer. Avian leukosis virus Subgroup J (ALV-J) is an oncogenic exogenous retrovirus, which induces severe immunosuppression and development of tumors in susceptible host. This study reveals for the first time that ALV-J inhibits autophagy through the envelope protein gp37. Here we demonstrate that envelope protein gp37 blocks the fusion of autophagosomes to lysosomes and induces incomplete autophagy. Interestingly, additional experiments revealed that the host chaperone protein TCP1 is also an autophagy inhibitor and blocking the process of autophagic flow in DF-1 cells. Through immunoprecipitation assays, we found that TCP1 interacts with gp37. In addition, TCP1 knockdown also abolished gp37-mediated inhibition of autophagy in DF-1 cells. Furthermore, TCP1 mediates gp37 of ALV-J to inhibit autophagy through activating AKT for promoting viral replication in DF-1 cells. • ALV-J inhibits autophagy through the envelope protein gp37 in DF-1 cells. • gp37 blocks the fusion of autophagosomes to lysosomes and induces incomplete autophagy in DF-1 cells. • TCP1 mediates gp37 of ALV-J to inhibit autophagy through activating AKT for promoting viral replication in DF-1 cells.