ORF3b

amino acid residues compared to 153–155 in SARS-CoV.^[1][2] Both the longer SARS-CoV and shorter SARS-CoV-2 proteins have been reported as interferon antagonists.^[2] It is unclear whether the SARS-CoV-2 gene expresses a functional protein.^[3]

codons. In SARS-CoV-2, the homologous region of the genome includes several stop codons in the same reading frame, resulting in a truncated gene of 22 codons. As a result, some papers have used the term "ORF3b" to refer to a later ORF with 57 codons.^[1] Exacerbating the confusion, both the 57-codon protein product^[4] and the 22-codon protein product^[2] have been described to have similar effects as interferon antagonists.^[1] In addition, the putative product of yet a third ORF of 41 codons has at least once been described as "3b protein".^[5][1] Numerous publications on SARS-CoV-2 refer ambiguously to "ORF3b".^[1]

5' end of ORF3b in SARS-CoV. The term ORF3c is used for the 41-codon gene and the term ORF3d is used for the 57-codon gene.^[1]

SARSr-CoV species.^[3]

mitochondria.^[8] It is not essential for viral replication.^[8]

subgenomic RNA, ribosome profiling, and comparative genomics have all been used to examine the functional gene content of SARS-CoV-2 and found little evidence that ORF3b expresses a functional protein.^[3] The SARS-CoV-2 protein has been reported to localize primarily to the cytosol when expressed in cell culture.^[2] Truncated forms of the protein from bat coronaviruses are also reportedly cytosolic, likely due to loss of the C-terminal nuclear localization sequence.^[7]

type I interferon response through inhibition of IRF3.^[8] Studies of the truncated SARS-CoV-2 ORF3b protein in cell culture suggest it is a more potent interferon antagonist than the SARS-CoV protein, which may be related to its length and to differences in subcellular localization.^[2]

signaling pathways.^[10][8]