SARS-CoV-2 nsp12 attenuates type I interferon production by inhibiting IRF3 nuclear translocation.
Cell Mol Immunol
; 18(4): 945-953, 2021 04.
Article
in English
| MEDLINE | ID: covidwho-1104474
ABSTRACT
SARS-CoV-2 is the pathogenic agent of COVID-19, which has evolved into a global pandemic. Compared with some other respiratory RNA viruses, SARS-CoV-2 is a poor inducer of type I interferon (IFN). Here, we report that SARS-CoV-2 nsp12, the viral RNA-dependent RNA polymerase (RdRp), suppresses host antiviral responses. SARS-CoV-2 nsp12 attenuated Sendai virus (SeV)- or poly(IC)-induced IFN-ß promoter activation in a dose-dependent manner. It also inhibited IFN promoter activation triggered by RIG-I, MDA5, MAVS, and IRF3 overexpression. Nsp12 did not impair IRF3 phosphorylation but suppressed the nuclear translocation of IRF3. Mutational analyses suggested that this suppression was not dependent on the polymerase activity of nsp12. Given these findings, our study reveals that SARS-CoV-2 RdRp can antagonize host antiviral innate immunity and thus provides insights into viral pathogenesis.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Interferon Type I
/
Interferon Regulatory Factor-3
/
Coronavirus RNA-Dependent RNA Polymerase
/
SARS-CoV-2
/
COVID-19
Limits:
Humans
Language:
English
Journal:
Cell Mol Immunol
Journal subject:
Allergy and Immunology
Year:
2021
Document Type:
Article
Similar
MEDLINE
...
LILACS
LIS