ORF8

Betacoronavirus NS8 protein
The SARS-CoV-2 ORF8 protein dimer. Internal disulfide bonds are shown in yellow and the intermolecular disulfide is shown in magenta. From PDB: 7JTL​.[1]
Identifiers
SymbolbCoV_NS8
PfamPF12093
InterProIPR022722
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary

ORF8 is a gene that encodes a viral accessory protein, Betacoronavirus NS8 protein, in coronaviruses of the subgenus Sarbecovirus. It is one of the least well conserved and most variable parts of the genome.[2][3][4][5] In some viruses, a deletion splits the region into two smaller open reading frames, called ORF8a and ORF8b - a feature present in many SARS-CoV viral isolates from later in the SARS epidemic, as well as in some bat coronaviruses.[4][3] For this reason the full-length gene and its protein are sometimes called ORF8ab.[3][6] The full-length gene, exemplified in SARS-CoV-2, encodes a protein with an immunoglobulin domain of unknown function, possibly involving interactions with the host immune system.[4][3][1] It is similar in structure to the ORF7a protein, suggesting it may have originated through gene duplication.[7][8]

  1. ^ a b Flower TG, Buffalo CZ, Hooy RM, Allaire M, Ren X, Hurley JH (January 2021). "Structure of SARS-CoV-2 ORF8, a rapidly evolving immune evasion protein". Proceedings of the National Academy of Sciences of the United States of America. 118 (2): e2021785118. Bibcode:2021PNAS..11821785F. doi:10.1073/pnas.2021785118. PMC 7812859. PMID 33361333.
  2. ^ Tan Y, Schneider T, Leong M, Aravind L, Zhang D (May 2020). "Novel Immunoglobulin Domain Proteins Provide Insights into Evolution and Pathogenesis of SARS-CoV-2-Related Viruses". mBio. 11 (3). doi:10.1128/mBio.00760-20. PMC 7267882. PMID 32471829.
  3. ^ a b c d Zinzula L (January 2021). "Lost in deletion: The enigmatic ORF8 protein of SARS-CoV-2". Biochemical and Biophysical Research Communications. 538: 116–124. doi:10.1016/j.bbrc.2020.10.045. PMC 7577707. PMID 33685621.
  4. ^ a b c Redondo N, Zaldívar-López S, Garrido JJ, Montoya M (7 July 2021). "SARS-CoV-2 Accessory Proteins in Viral Pathogenesis: Knowns and Unknowns". Frontiers in Immunology. 12: 708264. doi:10.3389/fimmu.2021.708264. hdl:10261/249329. PMC 8293742. PMID 34305949.
  5. ^ Forni D, Cagliani R, Clerici M, Sironi M (January 2017). "Molecular Evolution of Human Coronavirus Genomes". Trends in Microbiology. 25 (1): 35–48. doi:10.1016/j.tim.2016.09.001. PMC 7111218. PMID 27743750.
  6. ^ Liu DX, Fung TS, Chong KK, Shukla A, Hilgenfeld R (September 2014). "Accessory proteins of SARS-CoV and other coronaviruses". Antiviral Research. 109: 97–109. doi:10.1016/j.antiviral.2014.06.013. PMC 7113789. PMID 24995382.
  7. ^ Mariano G, Farthing RJ, Lale-Farjat SL, Bergeron JR (17 December 2020). "Structural Characterization of SARS-CoV-2: Where We Are, and Where We Need to Be". Frontiers in Molecular Biosciences. 7: 605236. doi:10.3389/fmolb.2020.605236. PMC 7773825. PMID 33392262.
  8. ^ Neches RY, Kyrpides NC, Ouzounis CA (January 2021). "Atypical Divergence of SARS-CoV-2 Orf8 from Orf7a within the Coronavirus Lineage Suggests Potential Stealthy Viral Strategies in Immune Evasion". mBio. 12 (1). doi:10.1128/mBio.03014-20. PMC 7845636. PMID 33468697.

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