Selective autophagy receptor SQSTM1/p62 inhibits Seneca Valley virus replication by targeting viral VP1 and VP3
Selective autophagy receptor SQSTM1/p62 inhibits Seneca Valley virus replication by targeting viral VP1 and VP3
复制标题
选择性自噬受体 SQSTM1/p62 通过靶向病毒 VP1 和 VP3 抑制塞内卡谷病毒复制
DOI：
10.1080/15548627.2021.1897223
复制
发表时间：
2021-03-14
期刊：
影响因子：
13.3
通讯作者：
Qian, Ping
中科院分区：
文献类型：
--
作者：
Wen, Wei;Li, Xiangmin;Qian, Ping
摘要自噬通过靶向病毒和启动宿主免疫应答在抗病毒免疫中起着关键作用。受体蛋白SQSTM 1/p62（隔离体1）在选择性自噬中起着至关重要的作用。它作为受体靶向泛素化蛋白质或病原体的吞噬细胞降解。本研究探讨了选择性自噬受体SQSTM 1与Seneca Valley病毒（SVV）之间的相互调节作用。SVV感染诱导自噬。自噬在猪细胞中促进SVV感染，但在人类细胞中发挥相反的功能。SQSTM 1的过表达降低了病毒蛋白的产生并降低了病毒滴度。进一步研究表明SQSTM 1与SVV VP 1和VP 3的相互作用不依赖于其乌巴结构域。SQSTM 1将SVV VP 1和VP 3靶向吞噬细胞进行降解以抑制病毒复制。为了抵消这一点，SVV进化出策略来绕过宿主自噬机制以促进病毒复制。SVV 3Cpro靶向受体SQSTM 1在谷氨酸355、谷氨酰胺392和谷氨酰胺395处裂解，并消除其介导选择性自噬的能力。同时，3Cpro介导的SQSTM 1切割产物失去了抑制病毒繁殖的能力。总的来说，我们的研究结果提供了宿主对病毒的选择性自噬的证据，并揭示了潜在的病毒策略，以逃避自噬机制的成功发病机制。缩略语：Baf.A1:巴弗洛霉素A1; Co-IP：免疫共沉淀; hpi：感染后h; LIR：LC 3相互作用区; MAP1LC3B/LC3B：微管相关蛋白1轻链3 β; MOI：感染复数; PB 1：N-末端Phox/Bem 1 p; Rap.：雷帕霉素;塞内卡谷病毒：SVV; SQSTM 1/p62：数据类型隔离体1; SQSTM 1-N355：SQSTM 1的残基1至355; SQSTM 1-C355：SQSTM 1的残基355至478; SQSTM 1-N392：SQSTM 1的残基1至392; SQSTM 1-C392：SQSTM 1的残基392至478; SQSTM 1-N388：SQSTM 1的残基1至388; SQSTM 1-N397：SQSTM 1的残基1至397;乌巴：泛素结合; Ubi：泛素。
ABSTRACT Macroautophagy/autophagy plays a critical role in antiviral immunity through targeting viruses and initiating host immune responses. The receptor protein, SQSTM1/p62 (sequestosome 1), plays a vital role in selective autophagy. It serves as a receptor targeting ubiquitinated proteins or pathogens to phagophores for degradation. In this study, we explored the reciprocal regulation between selective autophagy receptor SQSTM1 and Seneca Valley virus (SVV). SVV infection induced autophagy. Autophagy promoted SVV infection in pig cells but played opposite functions in human cells. Overexpression of SQSTM1 decreased viral protein production and reduced viral titers. Further study showed that SQSTM1 interacted with SVV VP1 and VP3 independent of its UBA domain. SQSTM1 targeted SVV VP1 and VP3 to phagophores for degradation to inhibit viral replication. To counteract this, SVV evolved strategies to circumvent the host autophagic machinery to promote viral replication. SVV 3Cpro targeted the receptor SQSTM1 for cleavage at glutamic acid 355, glutamine 392, and glutamine 395 and abolished its capacity to mediate selective autophagy. At the same time, the 3Cpro-mediated SQSTM1 cleavage products lost the ability to inhibit viral propagation. Collectively, our results provide evidence for selective autophagy in host against viruses and reveal potential viral strategies to evade autophagic machinery for successful pathogenesis. Abbreviations: Baf.A1: bafilomycin A1; Co-IP: co-immunoprecipitation; hpi: h post-infection; LIR: LC3-interacting region; MAP1LC3B/LC3B: microtubule-associated protein 1 light chain 3 beta; MOI: multiplicity of infection; PB1: N-terminal Phox/Bem1p; Rap.: rapamycin; Seneca Valley virus: SVV; SQSTM1/p62: sequestosome 1; SQSTM1-N355: residues 1 to 355 of SQSTM1; SQSTM1-C355: residues 355 to 478 of SQSTM1; SQSTM1-N392: residues 1 to 392 of SQSTM1; SQSTM1-C392: residues 392 to 478 of SQSTM1; SQSTM1-N388: residues 1 to 388 of SQSTM1; SQSTM1-N397: residues 1 to 397 of SQSTM1; UBA: ubiquitin association; Ubi: ubiquitin.