tetano
Editor, Senior Moderator
Cell Rep
. 2020 Sep 19;108234.
doi: 10.1016/j.celrep.2020.108234. Online ahead of print.
Evasion of Type I Interferon by SARS-CoV-2
Hongjie Xia[SUP] 1 [/SUP], Zengguo Cao[SUP] 2 [/SUP], Xuping Xie[SUP] 3 [/SUP], Xianwen Zhang[SUP] 3 [/SUP], John Yun-Chung Chen[SUP] 3 [/SUP], Hualei Wang[SUP] 4 [/SUP], Vineet D Menachery[SUP] 5 [/SUP], Ricardo Rajsbaum[SUP] 6 [/SUP], Pei-Yong Shi[SUP] 7 [/SUP]
Affiliations
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication and host immune response determine coronavirus disease 2019 (COVID-19), but studies evaluating viral evasion of immune response are lacking. Here, we use unbiased screening to identify SARS-CoV-2 proteins that antagonize type I interferon (IFN-I) response. We found three proteins that antagonize IFN-I production via distinct mechanisms: nonstructural protein 6 (nsp6) binds TANK binding kinase 1 (TBK1) to suppress interferon regulatory factor 3 (IRF3) phosphorylation, nsp13 binds and blocks TBK1 phosphorylation, and open reading frame 6 (ORF6) binds importin Karyopherin α 2 (KPNA2) to inhibit IRF3 nuclear translocation. We identify two sets of viral proteins that antagonize IFN-I signaling through blocking signal transducer and activator of transcription 1 (STAT1)/STAT2 phosphorylation or nuclear translocation. Remarkably, SARS-CoV-2 nsp1 and nsp6 suppress IFN-I signaling more efficiently than SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV). Thus, when treated with IFN-I, a SARS-CoV-2 replicon replicates to a higher level than chimeric replicons containing nsp1 or nsp6 from SARS-CoV or MERS-CoV. Altogether, the study provides insights on SARS-CoV-2 evasion of IFN-I response and its potential impact on viral transmission and pathogenesis.
Keywords: COVID-19; SARS-CoV-2; coronavirus disease 2019; immune evasion; interferon; replicon; severe acute respiratory syndrome coronavirus 2.
. 2020 Sep 19;108234.
doi: 10.1016/j.celrep.2020.108234. Online ahead of print.
Evasion of Type I Interferon by SARS-CoV-2
Hongjie Xia[SUP] 1 [/SUP], Zengguo Cao[SUP] 2 [/SUP], Xuping Xie[SUP] 3 [/SUP], Xianwen Zhang[SUP] 3 [/SUP], John Yun-Chung Chen[SUP] 3 [/SUP], Hualei Wang[SUP] 4 [/SUP], Vineet D Menachery[SUP] 5 [/SUP], Ricardo Rajsbaum[SUP] 6 [/SUP], Pei-Yong Shi[SUP] 7 [/SUP]
Affiliations
- PMID: 32979938
- DOI: 10.1016/j.celrep.2020.108234
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication and host immune response determine coronavirus disease 2019 (COVID-19), but studies evaluating viral evasion of immune response are lacking. Here, we use unbiased screening to identify SARS-CoV-2 proteins that antagonize type I interferon (IFN-I) response. We found three proteins that antagonize IFN-I production via distinct mechanisms: nonstructural protein 6 (nsp6) binds TANK binding kinase 1 (TBK1) to suppress interferon regulatory factor 3 (IRF3) phosphorylation, nsp13 binds and blocks TBK1 phosphorylation, and open reading frame 6 (ORF6) binds importin Karyopherin α 2 (KPNA2) to inhibit IRF3 nuclear translocation. We identify two sets of viral proteins that antagonize IFN-I signaling through blocking signal transducer and activator of transcription 1 (STAT1)/STAT2 phosphorylation or nuclear translocation. Remarkably, SARS-CoV-2 nsp1 and nsp6 suppress IFN-I signaling more efficiently than SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV). Thus, when treated with IFN-I, a SARS-CoV-2 replicon replicates to a higher level than chimeric replicons containing nsp1 or nsp6 from SARS-CoV or MERS-CoV. Altogether, the study provides insights on SARS-CoV-2 evasion of IFN-I response and its potential impact on viral transmission and pathogenesis.
Keywords: COVID-19; SARS-CoV-2; coronavirus disease 2019; immune evasion; interferon; replicon; severe acute respiratory syndrome coronavirus 2.