tetano
Editor, Senior Moderator
PLoS One
. 2021 Jun 24;16(6):e0253089.
doi: 10.1371/journal.pone.0253089. eCollection 2021.
SARS-CoV-2 viral proteins NSP1 and NSP13 inhibit interferon activation through distinct mechanisms
Christine Vazquez[SUP] 1 [/SUP], Sydnie E Swanson[SUP] 1 [/SUP], Seble G Negatu[SUP] 1 [/SUP], Mark Dittmar[SUP] 2 [/SUP], Jesse Miller[SUP] 2 [/SUP], Holly R Ramage[SUP] 3 [/SUP], Sara Cherry[SUP] 2 [/SUP], Kellie A Jurado[SUP] 1 [/SUP]
Affiliations
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a devastating global pandemic, infecting over 43 million people and claiming over 1 million lives, with these numbers increasing daily. Therefore, there is urgent need to understand the molecular mechanisms governing SARS-CoV-2 pathogenesis, immune evasion, and disease progression. Here, we show that SARS-CoV-2 can block IRF3 and NF-κB activation early during virus infection. We also identify that the SARS-CoV-2 viral proteins NSP1 and NSP13 can block interferon activation via distinct mechanisms. NSP1 antagonizes interferon signaling by suppressing host mRNA translation, while NSP13 downregulates interferon and NF-κB promoter signaling by limiting TBK1 and IRF3 activation, as phospho-TBK1 and phospho-IRF3 protein levels are reduced with increasing levels of NSP13 protein expression. NSP13 can also reduce NF-κB activation by both limiting NF-κB phosphorylation and nuclear translocation. Last, we also show that NSP13 binds to TBK1 and downregulates IFIT1 protein expression. Collectively, these data illustrate that SARS-CoV-2 bypasses multiple innate immune activation pathways through distinct mechanisms.
. 2021 Jun 24;16(6):e0253089.
doi: 10.1371/journal.pone.0253089. eCollection 2021.
SARS-CoV-2 viral proteins NSP1 and NSP13 inhibit interferon activation through distinct mechanisms
Christine Vazquez[SUP] 1 [/SUP], Sydnie E Swanson[SUP] 1 [/SUP], Seble G Negatu[SUP] 1 [/SUP], Mark Dittmar[SUP] 2 [/SUP], Jesse Miller[SUP] 2 [/SUP], Holly R Ramage[SUP] 3 [/SUP], Sara Cherry[SUP] 2 [/SUP], Kellie A Jurado[SUP] 1 [/SUP]
Affiliations
- PMID: 34166398
- DOI: 10.1371/journal.pone.0253089
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a devastating global pandemic, infecting over 43 million people and claiming over 1 million lives, with these numbers increasing daily. Therefore, there is urgent need to understand the molecular mechanisms governing SARS-CoV-2 pathogenesis, immune evasion, and disease progression. Here, we show that SARS-CoV-2 can block IRF3 and NF-κB activation early during virus infection. We also identify that the SARS-CoV-2 viral proteins NSP1 and NSP13 can block interferon activation via distinct mechanisms. NSP1 antagonizes interferon signaling by suppressing host mRNA translation, while NSP13 downregulates interferon and NF-κB promoter signaling by limiting TBK1 and IRF3 activation, as phospho-TBK1 and phospho-IRF3 protein levels are reduced with increasing levels of NSP13 protein expression. NSP13 can also reduce NF-κB activation by both limiting NF-κB phosphorylation and nuclear translocation. Last, we also show that NSP13 binds to TBK1 and downregulates IFIT1 protein expression. Collectively, these data illustrate that SARS-CoV-2 bypasses multiple innate immune activation pathways through distinct mechanisms.