Suppression of type I and type III IFN signalling by NSs protein of severe fever with thrombocytopenia syndrome virus through inhibition of STAT1 phosphorylation and activation.
Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging tick-borne pathogen causing significant morbidity and mortality in Asia. NSs protein of SFTSV is known to perturb type I IFN induction and signalling, but the mechanism remains to be fully understood. Here, we showed the suppression of both type I and type III IFN signalling by SFTSV NSs protein is mediated through inhibition of STAT1 phosphorylation and activation. Infection with live SFTSV or expression of NSs potently suppressed IFN-stimulated genes but not NFkB activation. NSs was capable of counteracting the activity of IFN-α1, IFN-β, IFN-λ1 and IFN-λ2. Mechanistically, NSs associated with STAT1 and STAT2, mitigated IFN-β-induced phosphorylation of STAT1 at S727, and reduced the expression and activity of STAT1 protein in IFN-β-treated cells, resulting in the inhibition of STAT1 and STAT2 recruitment to IFNstimulated promoters. Taken together, SFTSV NSs protein is an IFN antagonist that suppresses phosphorylation and activation of STAT1.
School of Biomedical Sciences, The University of Hong Kong, Pokfulam, Hong Kong.
Vidyanath
V
Chaudhary
Key Laboratory for Medical Virology and National Institute for Viral Disease Control and Prevention, Chinese Centre for Disease Control and Prevention, Beijing 102206, PR China.
Shuo
S
Zhang
School of Biomedical Sciences, The University of Hong Kong, Pokfulam, Hong Kong.
Kit-San
KS
Yuen
Key Laboratory for Medical Virology and National Institute for Viral Disease Control and Prevention, Chinese Centre for Disease Control and Prevention, Beijing 102206, PR China.
Chuan
C
Li
School of Biomedical Sciences, The University of Hong Kong, Pokfulam, Hong Kong.
Pak-Yin
PY
Lui
School of Biomedical Sciences, The University of Hong Kong, Pokfulam, Hong Kong.
Sin-Yee
SY
Fung
School of Biomedical Sciences, The University of Hong Kong, Pokfulam, Hong Kong.
Pei-Hui
PH
Wang
School of Biomedical Sciences, The University of Hong Kong, Pokfulam, Hong Kong.
Chi-Ping
CP
Chan
Key Laboratory for Medical Virology and National Institute for Viral Disease Control and Prevention, Chinese Centre for Disease Control and Prevention, Beijing 102206, PR China.
Dexin
D
Li
Department of Microbiology, The University of Hong Kong, Pokfulam, Hong Kong.
Kin-Hang
KH
Kok
Key Laboratory for Medical Virology and National Institute for Viral Disease Control and Prevention, Chinese Centre for Disease Control and Prevention, Beijing 102206, PR China.
Mifang
M
Liang
School of Biomedical Sciences, The University of Hong Kong, Pokfulam, Hong Kong.
Dong-Yan
DY
Jin
D006801:Humans; D016898:Interferon-alpha / Q000235:genetics* / Q000378:metabolism; D016899:Interferon-beta / Q000235:genetics* / Q000378:metabolism; D007372:Interferons; D007378:Interleukins / Q000235:genetics* / Q000378:metabolism; D010217:Phlebotomus Fever / Q000235:genetics* / Q000378:metabolism / Q000821:virology; D016856:Phlebovirus / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D050794:STAT1 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D050795:STAT2 Transcription Factor / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000378:metabolism*; D000095022:Interferon Lambda
D016898:Interferon-alpha; D016899:Interferon-beta; D007372:Interferons; D007378:Interleukins; D050794:STAT1 Transcription Factor; D050795:STAT2 Transcription Factor; D017361:Viral Nonstructural Proteins; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C494079:STAT1 protein, human