Document Type
Article
Publication Date
6-24-2021
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 phosphoIRF3 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.
Recommended Citation
Vazquez, Christine; Swanson, Sydnie E; Negatu, Seble G; Dittmar, Mark; Miller, Jesse; Ramage, Holly; Cherry, Sara; and Jurado, Kellie A, "SARS-CoV-2 viral proteins NSP1 and NSP13 inhibit interferon activation through distinct mechanisms" (2021). Department of Microbiology and Immunology Faculty Papers. Paper 127.
https://jdc.jefferson.edu/mifp/127
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
PubMed ID
34166398
Language
English
Comments
This article is the author’s final published version in PLoS ONE, Volume 16, Issue 6 June 2021, Article number e0253089.
The published version is available at https://doi.org/10.1371/journal.pone.0253089. Copyright © Vazquez et al.