ORF7a

A number of possible functions for the ORF7a protein have been described. The primary function is thought to be immunomodulation and interferon antagonism. The protein is not essential for viral replication. It is unclear if this occurs in SARS-CoV-2. It has also been reported to induce apoptosis via a caspase dependent pathway. Also, it contains a motif which has been demonstrated to mediate COPII dependent transport out of the endoplasmic reticulum, and the protein is targeted to the Golgi apparatus. In SARS-CoV-2, ORF7a protein has been described as an effective interferon antagonist. The SARS-CoV-2 protein may have immunomodulatory effects through interaction with monocytes. ==Structure==

The ORF7a protein is a transmembrane protein with 121 amino acid residues in SARS-CoV-2 and 122 in SARS-CoV. ==Expression and localization==

Along with the genes for other viral accessory proteins, the ORF7a gene is located near those encoding the viral structural proteins, at the 5' end of the coronavirus RNA genome. In SARS-CoV, subcellular localization to the endoplasmic reticulum, Golgi apparatus, and ERGIC has been reported, ==Evolution==

topologies. It is thought that ORF8 in SARS-CoV-2, which encodes a protein with a similar Ig-like fold, may be a paralog of ORF7a that originated through gene duplication, though some bioinformatics analyses suggest the similarity may be too low to support duplication, which is relatively uncommon in viruses. Immunoglobulin domains are uncommon in coronaviruses; other than the subset of betacoronaviruses with ORF8 and ORF7a, only a small number of bat alphacoronaviruses have been identified as containing likely Ig domains, while they are absent from gammacoronaviruses and deltacoronaviruses. The beta and alpha Ig domains may be independent acquisitions, where ORF8 and ORF7a may have been acquired from host proteins. nonsense mutations (introducing a premature stop codon and truncating the protein), and at least one gene fusion. Recent analyses indicate that the repeated knockout of ORF8 in SARS-CoV-2 through deletion mutations is driven by positive selection, suggesting an adaptive advantage for the virus during human infection. The study showed ORF8 deletions were associated with less severe clinical disease. ==References==