Sarbecovirus ORF6 proteins hamper induction of interferon signaling.

ABSTRACT: The presence of an ORF6 gene distinguishes sarbecoviruses such as severe acute respiratory syndrome coronavirus (SARS-CoV) and SARS-CoV-2 from other betacoronaviruses. Here we show that ORF6 inhibits induction of innate immune signaling, including upregulation of type I interferon (IFN) upon viral infection as well as type I and III IFN signaling. Intriguingly, ORF6 proteins from SARS-CoV-2 lineages are more efficient antagonists of innate immunity than their orthologs from SARS-CoV lineages. Mutational analyses identified residues E46 and Q56 as important determinants of the antagonistic activity of SARS-CoV-2 ORF6. Moreover, we show that the anti-innate immune activity of ORF6 depends on its C-terminal region and that ORF6 inhibits nuclear translocation of IRF3. Finally, we identify natu

SUBMITTER: Kimura I 

PROVIDER: S-EPMC7953434 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature