TY - JOUR
T1 - Type I Interferon Susceptibility Distinguishes SARS-CoV-2 from SARS-CoV
AU - Lokugamage, Kumari G.
AU - Hage, Adam
AU - de Vries, Maren
AU - Valero-Jimenez, Ana M.
AU - Schindewolf, Craig
AU - Dittmann, Meike
AU - Rajsbaum, Ricardo
AU - Menachery, Vineet D.
N1 - Funding Information:
This research was supported by NIH grants from the National Institute on Aging (NIA) and the National Institute of Allergy and Infectious Diseases (NIAID) (U19AI100625 and R00AG049092 to V.D.M., R24AI120942 to WRCEVA, R01AI134907 to R.R., and 1R01AI143639-01 and 1R21AI139374-01 to M.D.), Jan Vilcek/David Goldfarb Fellowship Endowment Funds to A.M.V.-J., and NIH grant T32 AI007526 to A.H. This research was also supported by a STARs award provided by the University of Texas System to V.D.M. and trainee funding provided by the McLaughlin Fellowship Fund at UTMB.
Publisher Copyright:
Copyright © 2020 American Society for Microbiology. All Rights Reserved.
PY - 2020/12
Y1 - 2020/12
N2 - 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.
AB - 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.
KW - 2019-nCoV
KW - COVID-19
KW - Coronavirus
KW - IFN
KW - Interferon
KW - SARS-CoV
KW - SARS-CoV-2
KW - Type I interferon
UR - http://www.scopus.com/inward/record.url?scp=85092776169&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85092776169&partnerID=8YFLogxK
U2 - 10.1128/JVI.01410-20
DO - 10.1128/JVI.01410-20
M3 - Article
C2 - 32938761
AN - SCOPUS:85092776169
VL - 94
JO - Journal of Virology
JF - Journal of Virology
SN - 0022-538X
IS - 23
M1 - e01410
ER -