Two Conserved Amino Acids within the NSs of Severe Fever with Thrombocytopenia Syndrome Phlebovirus Are Essential for Anti-interferon Activity

Journal of Virology
Miyu MoriyamaTakeshi Ichinohe

Abstract

The nonstructural protein (NSs) of severe fever with thrombocytopenia syndrome phlebovirus (SFTSV) sequesters TANK-binding kinase 1 (TBK1) into NSs-induced cytoplasmic structures to inhibit the phosphorylation and nuclear translocation of interferon (IFN) regulatory factor 3 (IRF3) and subsequent interferon beta (IFN-β) production. Although the C-terminal region of SFTSV NSs (NSs66-249) has been linked to the formation of NSs-induced cytoplasmic structures and inhibition of host IFN-β responses, the role of the N-terminal region in antagonizing host antiviral responses remains to be defined. Here, we demonstrate that two conserved amino acids at positions 21 and 23 in the SFTSV and heartland virus (HRTV) NSs are essential for suppression of IRF3 phosphorylation and IFN-β mRNA expression following infection with SFTSV or recombinant influenza virus lacking the NS1 gene. Surprisingly, formation of SFTSV/HRTV NSs-induced cytoplasmic structures is not essential for inhibition of host antiviral responses. Rather, an association between SFTSV/HRTV NSs and TBK1 is required for suppression of mitochondrial antiviral signaling protein (MAVS)-mediated activation of IFN-β promoter activity. Although SFTSV NSs did not prevent the ubiquitin...Continue Reading

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Citations

Apr 2, 2019·Expert Opinion on Therapeutic Targets·Chunyuan Zhao, Wei Zhao
Dec 11, 2019·Proceedings of the National Academy of Sciences of the United States of America·Kwang-Min YuYoung Ki Choi
Jan 7, 2020·The Journal of Clinical Investigation·Tadaki SuzukiHideki Hasegawa
Oct 13, 2019·Nature Communications·Miyu MoriyamaTakeshi Ichinohe
Aug 14, 2020·Current Opinion in Virology·Carlos Diaz-Salazar, Joseph C Sun
Mar 7, 2021·Viruses·Shanna S LeventhalDavid W Hawman
Mar 13, 2021·Frontiers in Immunology·Jian-Wei LiuXue-Jie Yu
May 1, 2021·Viruses·Solène LerolleVincent Legros
Nov 18, 2021·PLoS Pathogens·Bin-Yan LiuChuan-Min Zhou

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