| Primary Identifier | IPR022722 | Type | Family |
| Short Name | ORF8_betacoronavirus |
| description | This entry includes the ORF8 gene products (also known as NS8, accessory protein 8) from human SARS coronavirus (SARS-CoV), SARS-CoV-2, Bat coronavirus HKU3 and pangolin coronaviruses [].ORF8 is an accessory protein that is not shared by all members of subgenus sarbecovirus. The presence and location of ORF8 in the SARS-CoV-2 genome has led its classification with SARS-CoV [, ]. ORF8 is a potential pathogenicity factor which evolves rapidly to counter the immune response and facilitate the transmission between hosts []. ORF8 has been suggested to be one of the relevant genes in the study of human adaptation of the virus [, ].The ORF8 protein is a fast-evolving protein in SARS-related CoVs, with a tendency to recombine and undergo deletions. During the early phases of the SARS (SARS-CoV) epidemic in 2002, human isolates were found to possess a unique continuous ORF8 with 366 nucleotides and a predicted protein with 122 amino acids. During the middle and late phases of the SARS epidemic, two functional ORFs (ORF8a and ORF8b) were emerged; they are predicted to encode two small proteins, 8a with 39 amino acids and 8b with 84 amino acids. Interestingly, SARS-CoV-2 ORF8 has not undergone any significantly measurable deletion events, so its function as a full-length protein might be more important to its pathogenicity []. ORF8 plays a role in modulating host immune response []which may act by down-regulating major histocompatibility complex class I (MHC-I) []. It may inhibit expression of some members of the IFN-stimulated gene (ISG) family including hosts IGF2BP1/ZBP1, MX1 and MX2, and DHX58 []. ORF8 also binds to IL17RA receptor, leading to IL17 pathway activation and an increased secretion of pro-inflammatory factors, contributing to cytokine storm during COVID-19 infection []. |
