Non-structural Proteins of Severe Fever With Thrombocytopenia Syndrome Virus Suppress RNA Synthesis in a Transcriptionally Active cDNA-Derived Viral RNA Synthesis System
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, whic...
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| Format: | Article |
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Frontiers Media S.A.
2021-08-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmicb.2021.709517/full |
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| author | Fuli Ren Fuli Ren Fuli Ren Shu Shen Shu Shen Yun-Jia Ning Yun-Jia Ning Qiongya Wang Shiyu Dai Shiyu Dai Junming Shi Junming Shi Min Zhou Min Zhou Hualin Wang Hualin Wang Chaolin Huang Chaolin Huang Ding-Yu Zhang Fei Deng Fei Deng |
| author_facet | Fuli Ren Fuli Ren Fuli Ren Shu Shen Shu Shen Yun-Jia Ning Yun-Jia Ning Qiongya Wang Shiyu Dai Shiyu Dai Junming Shi Junming Shi Min Zhou Min Zhou Hualin Wang Hualin Wang Chaolin Huang Chaolin Huang Ding-Yu Zhang Fei Deng Fei Deng |
| author_sort | Fuli Ren |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-21T23:21:51Z |
| format | Article |
| id | doaj.art-656adeea587a4b8190481e90f937f74a |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-12-21T23:21:51Z |
| publishDate | 2021-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-656adeea587a4b8190481e90f937f74a2022-12-21T18:46:47ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2021-08-011210.3389/fmicb.2021.709517709517Non-structural Proteins of Severe Fever With Thrombocytopenia Syndrome Virus Suppress RNA Synthesis in a Transcriptionally Active cDNA-Derived Viral RNA Synthesis SystemFuli Ren0Fuli Ren1Fuli Ren2Shu Shen3Shu Shen4Yun-Jia Ning5Yun-Jia Ning6Qiongya Wang7Shiyu Dai8Shiyu Dai9Junming Shi10Junming Shi11Min Zhou12Min Zhou13Hualin Wang14Hualin Wang15Chaolin Huang16Chaolin Huang17Ding-Yu Zhang18Fei Deng19Fei Deng20Research Center for Translational Medicine, Wuhan Jinyintan Hospital, Wuhan, ChinaState Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, ChinaNational Virus Resource Center, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, ChinaState Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, ChinaNational Virus Resource Center, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, ChinaState Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, ChinaNational Virus Resource Center, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, ChinaResearch Center for Translational Medicine, Wuhan Jinyintan Hospital, Wuhan, ChinaState Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, ChinaNational Virus Resource Center, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, ChinaState Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, ChinaNational Virus Resource Center, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, ChinaState Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, ChinaNational Virus Resource Center, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, ChinaState Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, ChinaNational Virus Resource Center, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, ChinaResearch Center for Translational Medicine, Wuhan Jinyintan Hospital, Wuhan, ChinaDepartment of Infectious Diseases, Wuhan Jinyintan Hospital, Wuhan, ChinaResearch Center for Translational Medicine, Wuhan Jinyintan Hospital, Wuhan, ChinaState Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, ChinaNational Virus Resource Center, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, ChinaSevere 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.https://www.frontiersin.org/articles/10.3389/fmicb.2021.709517/fullbunyavirusRNA synthesisHRTVSFTSV RNA synthesis and regulationNSsSFTSV |
| spellingShingle | Fuli Ren Fuli Ren Fuli Ren Shu Shen Shu Shen Yun-Jia Ning Yun-Jia Ning Qiongya Wang Shiyu Dai Shiyu Dai Junming Shi Junming Shi Min Zhou Min Zhou Hualin Wang Hualin Wang Chaolin Huang Chaolin Huang Ding-Yu Zhang Fei Deng Fei Deng Non-structural Proteins of Severe Fever With Thrombocytopenia Syndrome Virus Suppress RNA Synthesis in a Transcriptionally Active cDNA-Derived Viral RNA Synthesis System Frontiers in Microbiology bunyavirus RNA synthesis HRTV SFTSV RNA synthesis and regulation NSs SFTSV |
| title | Non-structural Proteins of Severe Fever With Thrombocytopenia Syndrome Virus Suppress RNA Synthesis in a Transcriptionally Active cDNA-Derived Viral RNA Synthesis System |
| title_full | Non-structural Proteins of Severe Fever With Thrombocytopenia Syndrome Virus Suppress RNA Synthesis in a Transcriptionally Active cDNA-Derived Viral RNA Synthesis System |
| title_fullStr | Non-structural Proteins of Severe Fever With Thrombocytopenia Syndrome Virus Suppress RNA Synthesis in a Transcriptionally Active cDNA-Derived Viral RNA Synthesis System |
| title_full_unstemmed | Non-structural Proteins of Severe Fever With Thrombocytopenia Syndrome Virus Suppress RNA Synthesis in a Transcriptionally Active cDNA-Derived Viral RNA Synthesis System |
| title_short | Non-structural Proteins of Severe Fever With Thrombocytopenia Syndrome Virus Suppress RNA Synthesis in a Transcriptionally Active cDNA-Derived Viral RNA Synthesis System |
| title_sort | non structural proteins of severe fever with thrombocytopenia syndrome virus suppress rna synthesis in a transcriptionally active cdna derived viral rna synthesis system |
| topic | bunyavirus RNA synthesis HRTV SFTSV RNA synthesis and regulation NSs SFTSV |
| url | https://www.frontiersin.org/articles/10.3389/fmicb.2021.709517/full |
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