ABSTRACT As an enveloped virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) contains a membrane protein (M) that mediates viral release from cellular membranes. However, the molecular mechanisms of SARS-CoV-2 virion release remain poorly understood. In the present study, we performed RNA interference (RNAi) screening and identified the E3 ligase RNF5, which mediates the ubiquitination of SARS-CoV-2 M at residue K15 to enhance the interaction of the viral envelope protein (E) with M, whereas the deubiquitinating enzyme POH1 negatively regulates this process. The M-E complex ensures the uniform size of viral particles for viral maturation and mediates virion release. Moreover, M traffics from the Golgi apparatus to autophagosomes and uses autophagosomes for virion release, and this process is dependent on RNF5-mediated ubiquitin modification and M-E interaction. These results demonstrate that ubiquitin modification of SARS-CoV-2 M stabilizes the M-E complex and uses autophagosomes for virion release.
【저자키워드】 SARS-CoV-2, Release, autophagy, virus-like particles, ubiquitination, RNF5, 【초록키워드】 coronavirus, molecular mechanism, virus, membrane protein, RNA interference, Interaction, regulate, viral envelope protein, acute respiratory syndrome, maturation, enzyme, complex, residue, virion, Modification, E3 ligase, Golgi apparatus, cellular membranes, viral particle, ENhance, performed, dependent on, 【제목키워드】 ubiquitin, Ligase,