Unknown

Dataset Information

0

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 naturally occurring frameshift/nonsense mutations that result in an inactivating truncation of ORF6 in approximately 0.2% of SARS-CoV-2 isolates. Our findings suggest that ORF6 contributes to the poor IFN activation observed in individuals with coronavirus disease 2019 (COVID-19).

SUBMITTER: Kimura I 

PROVIDER: S-EPMC7953434 | biostudies-literature |

REPOSITORIES: biostudies-literature

Similar Datasets

| S-EPMC7309931 | biostudies-literature
| S-EPMC7668094 | biostudies-literature
2020-10-20 | GSE159593 | GEO
| S-EPMC7473193 | biostudies-literature
| S-EPMC4020042 | biostudies-literature
| S-EPMC8636442 | biostudies-literature
| PRJNA706167 | ENA
| S-EPMC7996988 | biostudies-literature
| S-EPMC3488571 | biostudies-literature
| S-EPMC3930619 | biostudies-literature