title: Roles of viroplasm-like structures formed by nonstructural protein NSs in infection with severe fever with thrombocytopenia syndrome virus.
abstract: Severe fever with thrombocytopenia syndrome (SFTS) virus is an emerging bunyavirus that causes a hemorrhagic fever with a high mortality rate. The virus is likely tick-borne and replicates primarily in hemopoietic cells, which may lead to disregulation of proinflammatory cytokine induction and loss of leukocytes and platelets. The viral genome contains L, M, and S segments encoding a viral RNA polymerase, glycoproteins G(n) and G(c), nucleoprotein (NP), and a nonstructural S segment (NSs) protein. NSs protein is involved in the regulation of host innate immune responses and suppression of IFNβ-promoter activities. In this article, we demonstrate that NSs protein can form viroplasm-like structures (VLSs) in infected and transfected cells. NSs protein molecules interact with one another, interact with NP, and were associated with viral RNA in infected cells, suggesting that NSs protein may be involved in viral replication. Furthermore, we observed that NSs-formed VLS colocalized with lipid droplets and that inhibitors of fatty acid biosynthesis decreased VLS formation or viral replication in transfected and infected cells. Finally, we have demonstrated that viral dsRNAs were also localized in VLS in infected cells, suggesting that NSs-formed VLS may be implicated in the replication of SFTS bunyavirus. These findings identify a novel function of nonstructural NSs in SFTSV-infected cells where it is a scaffolding component in a VLS functioning as a virus replication factory. This function is in addition to the role of NSs protein in modulating host responses that will broaden our understanding of viral pathogenesis of phleboviruses.
authors.affiliation: Medical School, State Key Laboratory of Pharmaceutical Biotechnology, and Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing, China;
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Wu
authors.affiliation: Jiangsu Provincial Center for Disease Prevention and Control, Nanjing, China;
authors.forename: Xian
authors.initials: X
authors.lastname: Qi
authors.affiliation: China Center for Disease Prevention and Control, Beijing, China; and.
authors.forename: Mifang
authors.initials: M
authors.lastname: Liang
authors.affiliation: China Center for Disease Prevention and Control, Beijing, China; and.
authors.forename: Chuan
authors.initials: C
authors.lastname: Li
authors.affiliation: Veterinary and Biomedical Sciences, University of Minnesota-Twin Cities, St. Paul, Minnesota, USA.
authors.forename: Carol J
authors.initials: CJ
authors.lastname: Cardona
authors.affiliation: China Center for Disease Prevention and Control, Beijing, China; and.
authors.forename: Dexin
authors.initials: D
authors.lastname: Li
authors.affiliation: Medical School, State Key Laboratory of Pharmaceutical Biotechnology, and Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing, China; Veterinary and Biomedical Sciences, University of Minnesota-Twin Cities, St. Paul, Minnesota, USA zxing@umn.edu.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Xing
mesh_terms: D000818:Animals; D002044:Bunyaviridae Infections / Q000276:immunology / Q000821:virology*; D002522:Chlorocebus aethiops; D057809:HEK293 Cells; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D007181:Inclusion Bodies, Viral / Q000378:metabolism*; D050356:Lipid Metabolism; D009698:Nucleoproteins / Q000378:metabolism; D016856:Phlebovirus / Q000648:ultrastructure*; D012367:RNA, Viral / Q000235:genetics; D014709:Vero Cells; D017361:Viral Nonstructural Proteins / Q000378:metabolism*; D014779:Virus Replication / Q000502:physiology
chemical_list: C423923:NSs protein, Bunyamwera bunyavirus; D009698:Nucleoproteins; D012367:RNA, Viral; D017361:Viral Nonstructural Proteins
keywords: bunyavirus; nucleoprotein; viral replication