title: Synaptogyrin-2 Promotes Replication of a Novel Tick-borne Bunyavirus through Interacting with Viral Nonstructural Protein NSs.
abstract: Synaptogyrin-2 is a non-neuronal member of the synaptogyrin family involved in synaptic vesicle biogenesis and trafficking. Little is known about the function of synaptogyrin-2. Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease characterized by high fever, thrombocytopenia, and leukocytopenia with high mortality, caused by a novel tick-borne phlebovirus in the family Bunyaviridae. Our previous studies have shown that the viral nonstructural protein NSs forms inclusion bodies (IBs) that are involved in viral immune evasion, as well as viral RNA replication. In this study, we sought to elucidate the mechanism by which NSs formed the IBs, a lipid droplet-based structure confirmed by NSs co-localization with perilipin A and adipose differentiation-related protein (ADRP). Through a high throughput screening, we identified synaptogyrin-2 to be highly up-regulated in response to SFTS bunyavirus (SFTSV) infection and to be a promoter of viral replication. We demonstrated that synaptogyrin-2 interacted with NSs and was translocated into the IBs, which were reconstructed from lipid droplets into large structures in infection. Viral RNA replication decreased, and infectious virus titers were lowered significantly when synaptogyrin-2 was silenced in specific shRNA-expressing cells, which correlated with the reduced number of the large IBs restructured from regular lipid droplets. We hypothesize that synaptogyrin-2 is essential to promoting the formation of the IBs to become virus factories for viral RNA replication through its interaction with NSs. These findings unveil the function of synaptogyrin-2 as an enhancer in viral infection.
authors.affiliation: From the State Key Laboratory of Pharmaceutical Biotechnology and Medical School, Nanjing University, Nanjing 210093, China.
authors.forename: Qiyu
authors.initials: Q
authors.lastname: Sun
authors.affiliation: the Jiangsu Provincial Center for Disease Control and Prevention, Nanjing 210009, China.
authors.forename: Xian
authors.initials: X
authors.lastname: Qi
authors.affiliation: From the State Key Laboratory of Pharmaceutical Biotechnology and Medical School, Nanjing University, Nanjing 210093, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: From the State Key Laboratory of Pharmaceutical Biotechnology and Medical School, Nanjing University, Nanjing 210093, China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Wu
authors.affiliation: the National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China, and.
authors.forename: Mifang
authors.initials: M
authors.lastname: Liang
authors.affiliation: the National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China, and.
authors.forename: Chuan
authors.initials: C
authors.lastname: Li
authors.affiliation: the National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China, and.
authors.forename: Dexin
authors.initials: D
authors.lastname: Li
authors.affiliation: the Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, Twin Cities, St. Paul, Minnesota 55108.
authors.forename: Carol J
authors.initials: CJ
authors.lastname: Cardona
authors.affiliation: From the State Key Laboratory of Pharmaceutical Biotechnology and Medical School, Nanjing University, Nanjing 210093, China, the Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, Twin Cities, St. Paul, Minnesota 55108 zxing@umn.edu zxing@nju.edu.cn.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Xing
mesh_terms: D000818:Animals; D002044:Bunyaviridae Infections / Q000235:genetics / Q000378:metabolism*; D002522:Chlorocebus aethiops; D006367:HeLa Cells; D006801:Humans; D007181:Inclusion Bodies, Viral / Q000235:genetics / Q000378:metabolism / Q000821:virology; D016856:Phlebovirus / Q000502:physiology*; D012367:RNA, Viral / Q000096:biosynthesis / Q000235:genetics; D062805:Synaptogyrins / Q000235:genetics / Q000378:metabolism*; D017282:Tick-Borne Diseases / Q000235:genetics / Q000378:metabolism*; D014709:Vero Cells; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication / Q000502:physiology*
chemical_list: D012367:RNA, Viral; C569018:SYNGR2 protein, human; D062805:Synaptogyrins; D017361:Viral Nonstructural Proteins
keywords: lipid droplet; negative-strand RNA virus; protein-protein interaction; viral protein; viral replication