1. Selective autophagy receptor SQSTM1/ p62 inhibits Seneca Valley virus replication by targeting viral VP1 and VP3
- Author
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Huanchun Chen, Qiongqiong Zhao, Haoyuan Wang, Xiangmin Li, Mengge Yin, Zekai Zhao, Junjie Hu, Wenqiang Liu, Ping Qian, Liuxin Qin, Hui Li, and Wei Wen
- Subjects
0301 basic medicine ,Swine ,viruses ,animal diseases ,chemical and pharmacologic phenomena ,Picornaviridae ,Biology ,Virus Replication ,Cell Line ,Selective autophagy ,03 medical and health sciences ,Antiviral immunity ,Immune system ,Sequestosome 1 ,Species Specificity ,Sequestosome-1 Protein ,Autophagy ,Animals ,Humans ,3c protease ,education ,Receptor ,Molecular Biology ,Viral Structural Proteins ,education.field_of_study ,030102 biochemistry & molecular biology ,Cell Biology ,biochemical phenomena, metabolism, and nutrition ,Seneca Valley virus ,Cell biology ,HEK293 Cells ,030104 developmental biology ,bacteria ,Research Paper - 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 3C(pro) 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 3C(pro)-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 A(1); 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.
- Published
- 2021