| Primary Identifier | IPR044392 | Type | Family |
| Short Name | ORF8_Bat_SARS_CoV_Rf1-like |
| description | This subfamily includes the ORF8 immunoglobulin (Ig) domain proteins of bat coronavirus Rf1 (Bat SARS CoV Rf1) and Bat CoV 273/2005, which have been classified previously as type II ORF8 proteins.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 []. |
