ORF9

ORF9 is an accessory protein synthesized from an alternative reading frame in the N gene. At mitochondrial level, ORF9 promotes suppression of the activation of INF regulatory factors and NF-κB. ORF9 forms a symmetric dimer where the monomer interactions resemble a handshake. Dimer assembling creates a hydrophobic tunnel that can accomodate a long fatty acid chain. Thus, ORF9 could anchor itself to a lipidic membrane by internalizing one or more lipidic tails. SARS-CoV-2 ORF9b shares high homology with SARS-CoV-1 (72·45% protein identity).

Narrative

ORF9 is an accessory protein synthesized from an alternative reading frame in the N gene. This accessory protein is integrated in viral particles and therefore it can be considered a structural protein. This incorporation occurs in presence of E and M proteins, suggesting a potential interaction among these proteins (Bouvet et al. 2010) ORF9 localizes in mitochondria outer membrane, cytoplasm, nucleus, endoplasmic reticulum and lipid vesicles (Shi et al. 2014; Calvo et al. 2012; Moshynskyy et al. 2007; Meier et al. 2006). At mitochondrial level, ORF9 promotes the ubiquitination and degradation of dynamin-like protein (DRP1), thereby causing mitochondria to show an elongated phenotype (Shi et al. 2014). Here, ORF9 also interacts with mitochondrial antiviral signalling protein (MAVS) and poly(rC) binding protein 2 (PCBP2) (Shi et al. 2014). Thus, PCBP2 facilitates the ubiquitination of MAVS by AIP4, suppressing the activation of INF regulatory factors and NF-κB (Shi et al. 2014). Besides, interaction and colocalization between ORF9 and ORF6 have been suggested (Calvo et al. 2012), but the relevance of this interaction remains unknown.

Structural analysis and comparison with SARS-CoV-1 ORF9b – SARS-CoV-1 ORF9b is a small protein of 98 residues length. Meier et al.(2006) showed that ORF9 forms a symmetric dimer where the monomer interactions resemble a handshake. Dimer assembling creates a hydrophobic tunnel that can accomodate a long fatty acid chain. The authors suggest that ORF9 could anchor itself to a lipidic membrane by internalizing one or more lipidic tails. SARS-CoV-2 ORF9 shares high homology with SARS-CoV-1 (72·45% protein identity).