PMID- 34484148 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20210907 IS - 1664-302X (Print) IS - 1664-302X (Electronic) IS - 1664-302X (Linking) VI - 12 DP - 2021 TI - Non-structural Proteins of Severe Fever With Thrombocytopenia Syndrome Virus Suppress RNA Synthesis in a Transcriptionally Active cDNA-Derived Viral RNA Synthesis System. PG - 709517 LID - 10.3389/fmicb.2021.709517 [doi] LID - 709517 AB - Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by the tick-borne SFTS bunyavirus (SFTSV) resulting in a high fatality rate up to 30%. SFTSV is a negative-strand RNA virus containing three single-stranded RNA genome segments designated as L, M, and S, which respectively, encode the RNA-dependent RNA polymerase (RdRp), glycoproteins Gn and Gc, and nucleoprotein (N) and non-structural proteins (NSs). NSs can form inclusion bodies (IBs) in infected and transfected cells. A previous study has provided a clue that SFTSV NSs may be involved in virus-like or viral RNA synthesis; however, the details remain unclear. Our work described here reveals that SFTSV NSs can downregulate virus-like RNA synthesis in a dose-dependent manner within a cDNA-derived viral RNA synthesis system, i.e., minigenome (-) and minigenome (+) systems based on transfection, superinfection, and luciferase reporter activity determination; meanwhile, NSs also show a weak inhibitory effect on virus replication. By using co-immunoprecipitation (Co-IP) and RT-PCR combined with site-directed mutagenesis, we found that NSs suppress virus-like RNA or virus replication through interacting with N but not with RdRp, and the negative regulatory effect correlates closely with the IB structure it formed but is not associated with its role of antagonizing host innate immune responses. When the cytoplasmic structure of IB formed by SFTSV NSs was deprived, the inhibitory effect of NSs on virus-like RNA synthesis would weaken and even disappear. Similarly, we also evaluated other bandavirus NSs that cannot form IB in neither infected nor transfected cells, and the results showed that the NSs of Heartland bandavirus (HRTV) did not show a significant inhibitory effect on virus-like RNA synthesis within a minigenome system. Our findings provide experimental evidence that SFTSV NSs participate in regulating virus-like or viral RNA synthesis and the negative effect may be due to the NSs-N interaction. CI - Copyright (c) 2021 Ren, Shen, Ning, Wang, Dai, Shi, Zhou, Wang, Huang, Zhang and Deng. FAU - Ren, Fuli AU - Ren F AD - Research Center for Translational Medicine, Wuhan Jinyintan Hospital, Wuhan, China. AD - State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China. AD - National Virus Resource Center, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China. FAU - Shen, Shu AU - Shen S AD - State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China. AD - National Virus Resource Center, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China. FAU - Ning, Yun-Jia AU - Ning YJ AD - State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China. AD - National Virus Resource Center, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China. FAU - Wang, Qiongya AU - Wang Q AD - Research Center for Translational Medicine, Wuhan Jinyintan Hospital, Wuhan, China. FAU - Dai, Shiyu AU - Dai S AD - State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China. AD - National Virus Resource Center, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China. FAU - Shi, Junming AU - Shi J AD - State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China. AD - National Virus Resource Center, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China. FAU - Zhou, Min AU - Zhou M AD - State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China. AD - National Virus Resource Center, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China. FAU - Wang, Hualin AU - Wang H AD - State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China. AD - National Virus Resource Center, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China. FAU - Huang, Chaolin AU - Huang C AD - Research Center for Translational Medicine, Wuhan Jinyintan Hospital, Wuhan, China. AD - Department of Infectious Diseases, Wuhan Jinyintan Hospital, Wuhan, China. FAU - Zhang, Ding-Yu AU - Zhang DY AD - Research Center for Translational Medicine, Wuhan Jinyintan Hospital, Wuhan, China. FAU - Deng, Fei AU - Deng F AD - State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China. AD - National Virus Resource Center, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China. LA - eng PT - Journal Article DEP - 20210816 PL - Switzerland TA - Front Microbiol JT - Frontiers in microbiology JID - 101548977 PMC - PMC8415556 OTO - NOTNLM OT - HRTV OT - NSs OT - RNA synthesis OT - SFTSV OT - SFTSV RNA synthesis and regulation OT - bunyavirus OT - minigenome COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2021/09/07 06:00 MHDA- 2021/09/07 06:01 PMCR- 2021/08/16 CRDT- 2021/09/06 05:55 PHST- 2021/05/14 00:00 [received] PHST- 2021/07/23 00:00 [accepted] PHST- 2021/09/06 05:55 [entrez] PHST- 2021/09/07 06:00 [pubmed] PHST- 2021/09/07 06:01 [medline] PHST- 2021/08/16 00:00 [pmc-release] AID - 10.3389/fmicb.2021.709517 [doi] PST - epublish SO - Front Microbiol. 2021 Aug 16;12:709517. doi: 10.3389/fmicb.2021.709517. eCollection 2021.