Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 292, Issue 40, Pages 16722-16733Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M117.805127
Keywords
-
Categories
Funding
- National Natural Science Foundation of China [31621061, 31600144]
- strategic priority research program of the Chinese Academy of Sciences [XDPB0301]
- National Basic Research Program (973 Program) of China [2013CB911101]
- Science and Technology Basic Work Program [2013FY113500]
- National Key Research and Development Program of China [2016YFC1200400, 2016YFE0113500]
- European Union's Horizon 2020 project European Virus Archive goes global (EVAg) [653316]
- Hubei Provincial Natural Science Foundation of China [2016CFB124]
- One-Three-Five Research Program of Wuhan Institute of Virology
Ask authors/readers for more resources
Heartland virus (HRTV) is a pathogenic phlebovirus related to the severe fever with thrombocytopenia syndrome virus (SFTSV), another phlebovirus causing life-threatening disease in humans. Previous findings have suggested that SFTSV can antagonize the host interferon (IFN) system via viral nonstructural protein (NSs)-mediated sequestration of antiviral signaling proteins into NSs-induced inclusion bodies. However, whether and how HRTV counteracts the host innate immunity is unknown. Here, we report that HRTV NSs (HNSs) also antagonizes IFN and cytokine induction and bolsters viral replication, although no noticeable inclusion body formation was observed in HNSs-expressing cells. Furthermore, HNSs inhibited the virus-triggered activation of IFN-beta promoter by specifically targeting the IFN-stimulated response element but not the NF-kappa B response element. Consistently, HNSs blocked the phosphorylation and nuclear translocation of IFN regulatory factor 3 (IRF3, an IFN-stimulated response element-activating transcription factor). Reporter gene assays next showed that HNSs blockades the antiviral signaling mediated by RIG-I-like receptors likely at the level of TANK-binding kinase 1 (TBK1). Indeed, HNSs strongly interacts with TBK1 as indicated by confocal microscopy and pulldown analyses, and we also noted that the scaffold dimerization domain of TBK1 is required for the TBK1-HNSs interaction. Finally, pulldown assays demonstrated that HNSs expression dose-dependently diminishes a TBK1-IRF3 interaction, further explaining the mechanism for HNSs function. Collectively, these data suggest that HNSs, an antagonist of host innate immunity, interacts with TBK1 and thereby hinders the association of TBK1 with its substrate IRF3, thus blocking IRF3 activation and transcriptional induction of the cellular antiviral responses.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available