Severe acute respiratory syndrome coronavirus Envelope small membrane protein and similar proteins
This group contains the Envelope (E) small membrane protein of Severe acute respiratory syndrome (SARS) coronavirus (CoV) and SARS-CoV-2, also known as 2019 novel coronavirus (2019-nCoV) or COVID-19 virus, as well as E proteins from related CoVs. There are five essential genes in CoVs that result in the following gene products: Spike (S) protein, Membrane (M) glycoprotein, Nucleocapsid (N), Envelope (E) protein, and the Orf1ab (a large polyprotein known as replicase/protease); all are required to produce a structurally complete viral particle. The E protein is a small polypeptide (76-109 amino acids) that contains a single alpha-helical transmembrane domain. It plays a central role in virus morphogenesis and assembly. It acts as a viroporin and self-assembles in host membranes forming homopentameric protein-lipid pores that allow ion transport with poor selectivity. For some CoVs, such as mouse hepatitis virus (MHV) and SARS-CoV, deletion of the E gene did not completely abolish replication, but the virions were severely disabled from infecting new host cells with significantly reduced viral titers. In animal models, SARS-CoV lacking the E gene also showed significantly attenuated viral titers, likely due to its deficiency in suppressing host stress response and apoptosis induction. Moreover, the PDZ-binding motif (PBM) at the C-terminus of SARS-CoV E protein was shown to interact with a host PDZ protein called syntenin and lead to its relocation from nucleus to cytoplasm during SARS-CoV infection, thereby activating p38 kinase to induce the overexpression of inflammatory cytokines. Thus, the E protein is involved in both, viral replication and pathogenesis during CoV infection.
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