The E3 Ubiquitin Ligase RNF5 Facilitates SARS-CoV-2 Membrane Protein-Mediated Virion Release

Abstract

Enveloped virus particles are released from the membranes of host cells, and viral membrane proteins (M) are critical for this process. A better understanding of the molecular mechanisms of SARS-CoV-2 assembly and budding is critical for the development of antiviral therapies.

The Deubiquitinase USP29 Promotes SARS-CoV-2 Virulence by Preventing Proteasome Degradation of ORF9b

“…In contrast, the host also utilizes the ubiquitin-proteasome system (UPS) to destabilize viral proteins such as deubiquitination by the deubiquitinating enzyme (DUB) USP21 of the HIV-1 protein Tat, which leads to Tat instability ( 10 ). Recent reports have shown that the E3 ubiquitin ligases RNF5 and CRL2 (ZYG11B) are recruited by membrane protein and ORF10 protein of SARS-CoV-2, respectively; However, CRL2 is dispensable for SARS-CoV-2 infection ( 11 , 12 ). Guo et al reported that DUB USP13 is hijacked by SARS-CoV-2 nsp13 and prevents its degradation ( 13 ).…”

The life cycle and enigmatic egress of coronaviruses

“…In line with data obtained with other viruses, the role of secretory autophagy in CoV egress has also been considered (Yuan et al, 2022). However, the detailed mechanisms of this process, which until now have been predominantly described in the case of cytosolic proteins, remain poorly understood.…”

“…Interestingly, the biogenesis of the DMVs engages the machineries operating in autophagy (Blanchard & Roingeard, 2015;Twu et al, 2021), with possible additional contribution from peroxisomes (Cortese et al, 2020). The autophagic pathway has also been implicated as an egress route for SARS-CoV-2 virus particles in light of ubiquitination of the M protein (Yuan et al, 2022). Following replication and transcription of viral RNAs, the genomic and subgenomic mRNAs leave the DMVs, most likely through special pores (Wolff et al, 2020).…”

Structural proteins in the mechanisms of betacoronavirus virion assembly

“…As a result of this mechanism, the virion also includes a nucleocapsid, i.e., a complex of N protein with RNA. A similar functional advan tage of the Cterminus over the transmembrane seg ments of the protein molecule was observed in the assembly of SARSCoV2 virions [43]. The purpose of M protein binding to the nucleocapsid complex for this coronavirus is considered in [44]: the authors assume that this complex is a certain stabilizer of the Cterminus, which, in turn, ensures an increase in the number of formed virions.…”