Journal
MICROBES AND INFECTION
Volume 20, Issue 6, Pages 360-368Publisher
ELSEVIER
DOI: 10.1016/j.micinf.2018.05.007
Keywords
SFTSV; NSs; Interferon; JAK-STAT pathway; STAT2; Inclusion body
Categories
Funding
- JSPS KAKENHI grant [25460563, 26460553]
- Shiga University of Medical Science, Wajinkai
- Yakult Foundation, Japan
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The nonstructural protein NSs of severe fever with thrombocytopenia syndrome phlebovirus blocks type I interferon (IFN)-stimulated JAK-STAT signaling. However, there is continuing controversy as to whether NSs targets STAT1 or STAT2 or both for this blockade. The present study was designed to gain a further understanding of the blockade mechanism. Immunoprecipitation experiments revealed a stronger interaction of NSs with STAT2 than with any other component constituting the JAK-STAT pathway. Expression of NSs resulted in the formation of cytoplasmic inclusion bodies (IBs), and affected cytoplasmic distribution of STAT2. STAT2 was relocated to NSs-induced IBs. Consequently, NSs inhibited IFN-alpha-stimulated tyrosine phosphorylation and nuclear translocation of STAT2. These inhibitory effects as well as the signaling blockade activity were not observed in NSs mutant proteins lacking the STAT2-binding ability. In contrast, NSs affected neither subcellular distribution nor phosphorylation of STAT1 in response to IFN-alpha and IFN-gamma, demonstrating that NSs has little physical and functional interactions with STAT1. Taken together, these results suggest that NSs sequesters STAT2 into NSs-induced IBs, thereby blocking type I IFN JAK-STAT signaling. (C) 2018 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.
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