| Betacoronavirus NS6 protein | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Identifiers | |||||||||
| Symbol | bCoV_NS6 | ||||||||
| Pfam | PF12133 | ||||||||
| InterPro | IPR022736 | ||||||||
| |||||||||
ORF6 is agene that encodes aviral accessory protein incoronaviruses of thesubgenusSarbecovirus, includingSARS-CoV andSARS-CoV-2. It is not present inMERS-CoV. It is thought to reduce theimmune system response to viral infection throughinterferon antagonism.[1][2][3]
The ORF6 protein is fairly small at 63amino acid residues long inSARS-CoV[2] and 61 inSARS-CoV-2.[3] The ORF6 sequence is not wellconserved and it has a relatively lowsequence identity between the two viruses at about 66%.[4] It has anamphipathicN-terminalalpha helix that associates with themembrane, but is not atransmembrane protein. Its approximately 20-residueC-terminal tail ispolar and extends into thecytosol, and containssignal sequences forprotein trafficking.[1][2]
Like the genes for other accessory proteins, the ORF6 gene is located near those encoding thestructural proteins, at the5' end of the coronavirus RNA genome. Along withORF7a,ORF7b, andORF8, ORF6 is located between themembrane (M) andnucleocapsid (N) genes.[1][2][3] It islocalized to theendoplasmic reticulum andGolgi apparatus,[1][2][3] with studies in SARS-CoV-2 also indicating association withvesicles such asautophagosomes andlysosomes.[3]
The primary function of the ORF6 protein is thought to beimmunomodulation andinterferon antagonism. It is notessential forviral replication, though its absence appears to reduce replication efficiency.[1][2]
Studies inSARS-CoV suggest that the ORF6 protein exhibitsprotein-protein interactions with another viral accessory protein,ORF9b protein.[1][5] In SARS-CoV, but not inrecombinantmurine hepatitis virus, ORF6 protein has been detected invirus-like particles and maturevirions, suggesting it can be a minorviral structural protein.[1][2]
The ORF6 protein from both SARS-CoV and SARS-CoV-2 is aninterferon antagonist and thought to be involved inimmune evasion. Severalprotein-protein interactions withhost cell proteins have been described to mediate this effect. It has been reported to inhibitnuclear import of theSTATtranscription factor, inhibiting interferon activation.[1][3] Studies of SARS-CoV report this may be mediated by binding of ORF6 protein tokaryopherins.[1][4] In SARS-CoV-2, the ORF6 protein reportedly interacts withRAE1 andNUP98, blocking karyopherin interactions.[3][6]
