核心提示： 近日，我校钱平教授团队在塞内卡谷病毒研究上取得新进展，该研究揭示了选择性自噬抑制塞内卡谷病毒复制的新机制。

 南湖新闻网讯（通讯员 文威）近日，我校农业微生物学国家重点实验室、动科动医学院钱平教授团队在塞内卡谷病毒研究上取得新进展，该研究揭示了选择性自噬抑制塞内卡谷病毒复制的新机制。

 塞内卡谷病毒（Seneca Valley Virus，SVV）属于小RNA病毒科塞内卡谷病毒属中的一员，临床症状与口蹄疫类似，易引起成年猪口部和蹄部出现水泡及新生仔猪的大量死亡。SVV感染宿主细胞会诱导细胞自噬，宿主选择性自噬受体p62通过靶向病毒蛋白VP1和VP3到溶酶体而降解。为促进病毒复制，病毒蛋白常常也具备拮抗宿主抗病毒蛋白的作用。同时该研究阐明了SVV 3Cpro 通过在多位点切割p62蛋白进而抑制其介导选择性自噬的功能，该功能也具有抑制其抗病毒的效果。此外该研究还发现，在不同的宿主细胞中诱导细胞自噬对病毒的增殖起到不同作用。

 此外，钱平课题组在国内首次报道了SVV的分离(Qian et al., Virology J, 2016)，阐明了该病毒3Cpro抑制I型干扰素和应激颗粒产生的分子机制(Qian et al., Journal of Virology, 2017; Wen et al., Virology, 2019; Wen et al., Frontiers in immunology, 2020)，以及该病毒诱导细胞凋亡的机制(Liu et al., Frontiers in microbiology, 2019)，并从结构生物学上揭示了塞内卡谷病毒由其受体ANTXR1介导的吸附和脱衣壳机制(Cao et al., PNAS, 2018)。

 审核人：钱平

 英文摘要：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.

 论文链接：https://www.tandfonline.com/doi/full/10.1080/15548627.2021.1897223?src=