SARS-CoV-2 Orf6 hijacks Nup98 to block STAT nuclear import and antagonize interferon signaling

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the ongoing coronavirus disease 2019 (COVID-19) pandemic that is a serious global health problem. Evasion of IFN-mediated antiviral signaling is a common defense strategy that pathogenic viruses use to replicate and propagate in their host. In this study, we show that SARS-CoV-2 is able to efficiently block STAT1 and STAT2 nuclear translocation in order to impair transcriptional induction of IFN-stimulated genes (ISGs). Our results demonstrate that the viral accessory protein Orf6 exerts this anti-IFN activity. We found that SARS-CoV-2 Orf6 localizes at the nuclear pore complex (NPC) and directly interacts with Nup98-Rae1…

• CI
  Canadian Institutes of Health Research

  Award: 156030
• NI
  National Institute of General Medical Sciences

  Award: 5R35GM133743
• NI
  National Institute of Allergy and Infectious Diseases

  Awards: HHSN272201400008C, U19AI118610, U19AI135972, R01AI154635
• DS
  Defense Sciences Office, DARPA

  Award: HR0011-19-20020