Type I Interferon Susceptibility Distinguishes SARS-CoV-2 from SARS-CoV

Kumari G. Lokugamage, Adam Hage, Maren de Vries, Ana M. Valero-Jimenez, Craig Schindewolf, Meike Dittmann, Ricardo Rajsbaum, Vineet D. Menachery

Research output: Contribution to journalArticlepeer-review

47 Scopus citations


SARS-CoV-2, a novel coronavirus (CoV) that causes COVID-19, has recently emerged causing an ongoing outbreak of viral pneumonia around the world. While distinct from SARS-CoV, both group 2B CoVs share similar genome organization, origins to bat CoVs, and an arsenal of immune antagonists. In this report, we evaluate type I interferon (IFN-I) sensitivity of SARS-CoV-2 relative to the original SARS-CoV. Our results indicate that while SARS-CoV-2 maintains similar viral replication to SARS-CoV, the novel CoV is much more sensitive to IFN-I. In Vero E6 and in Calu3 cells, SARS-CoV-2 is substantially attenuated in the context of IFN-I pretreatment, whereas SARS-CoV is not. In line with these findings, SARS-CoV-2 fails to counteract phosphorylation of STAT1 and expression of ISG proteins, while SARS-CoV is able to suppress both. Comparing SARS-CoV-2 and influenza A virus in human airway epithelial cultures, we observe the absence of IFN-I stimulation by SARS-CoV-2 alone but detect the failure to counteract STAT1 phosphorylation upon IFN-I pretreatment, resulting in near ablation of SARS-CoV-2 infection. Next, we evaluated IFN-I treatment postinfection and found that SARS-CoV-2 was sensitive even after establishing infection. Finally, we examined homology between SARS-CoV and SARS-CoV-2 in viral proteins shown to be interferon antagonists. The absence of an equivalent open reading frame 3b (ORF3b) and genetic differences versus ORF6 suggest that the two key IFN-I antagonists may not maintain equivalent function in SARS-CoV-2. Together, the results identify key differences in susceptibility to IFN-I responses between SARS-CoV and SARS-CoV-2 that may help inform disease progression, treatment options, and animal model development.

Original languageEnglish (US)
Article numbere01410
JournalJournal of virology
Issue number23
StatePublished - Dec 2020


  • 2019-nCoV
  • COVID-19
  • Coronavirus
  • IFN
  • Interferon
  • SARS-CoV
  • SARS-CoV-2
  • Type I interferon

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology


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