The E3 ligase RNF5 restricts SARS-CoV-2 replication by targeting its envelope protein for degradation
作者机构：Departement of Infectious DiseasesInfectious Diseases and Pathogen Biology CenterInstitute of Virology and AIDS ResearchKey Laboratory of Organ Regeneration and Transplantation of The Ministry of EducationThe First Hospital of Jilin UniversityChangchunChina Research Unit of Key Technologies for Prevention and Control of Virus ZoonosesChinese Academy of Medical SciencesChangchun Veterinary Research InstituteChinese Academy of Agricultural SciencesChangchun 130000 JilinChina
出 版 物：《Signal Transduction and Targeted Therapy》 (信号转导与靶向治疗（英文）)
年 卷 期：2023年第8卷第3期
页 面：1175-1185页
核心收录：
学科分类：0710[理学-生物学] 1002[医学-临床医学] 10[医学]
基 金：We thank C.Y.Dai for providing critical reagents.We thank Qing Ding(Tsinghua University)for trVLP system.We thank the Department of Biobank,Division of Clinical Research for providing human tissues.This work was supported in part by funding from the National Key R&D Program of China(2021YFC2301900 and 2021YFC2301904) the National Natural Science Foundation of China(81930062 and 81672004 to WZ) the Science and Technology Department of Jilin Province(20190101003JH,20190201272JC,YDZJ202201ZYTS671,and YDZJ202201ZYTS587) the Key Laboratory of Molecular Virology,Jilin Province(20102209) CAMS Innovation Fund for Medical Sciences(2020-12M-5-001).
主 题：envelope acute respiratory
摘 要：The coronavirus disease 2019(COVID-19)pandemic caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has caused a severe global health crisis;its structural protein envelope(E)is critical for viral entry,budding,production,and induction of pathology which makes it a potential target for therapeutics against COVID-19.Here,we find that the E3 ligase RNF5 interacts with and catalyzes ubiquitination of E on the 63rd lysine,leading to its degradation by the ubiquitin-proteasome system(UPS).Importantly,RNF5-induced degradation of E inhibits SARS-CoV-2 replication and the RNF5 pharmacological activator Analog-1 alleviates disease development in a mouse infection model.We also found that RNF5 is distinctively expressed in different age groups and in patients displaying different disease severity,which may be exploited as a prognostic marker for COVID-19.Furthermore,RNF5 recognized the E protein from various SARS-CoV-2 strains and SARS-CoV,suggesting that targeting RNF5 is a broad-spectrum antiviral strategy.Our findings provide novel insights into the role of UPS in antagonizing SARS-CoV-2 replication,which opens new avenues for therapeutic intervention to combat the COVID-19 pandemic.
维普期刊数据库