2. Academic Validation
  3. Synaptogyrin-2 Promotes Replication of a Novel Tick-borne Bunyavirus through Interacting with Viral Nonstructural Protein NSs

Synaptogyrin-2 Promotes Replication of a Novel Tick-borne Bunyavirus through Interacting with Viral Nonstructural Protein NSs

  • J Biol Chem. 2016 Jul 29;291(31):16138-49. doi: 10.1074/jbc.M116.715599.
Qiyu Sun 1,  Xian Qi 2,  Yan Zhang 1,  Xiaodong Wu 1,  Mifang Liang 3,  Chuan Li 3,  Dexin Li 3,  Carol J Cardona 4,  Zheng Xing 5
Affiliations

Affiliations

  • 1 From the State Key Laboratory of Pharmaceutical Biotechnology and Medical School, Nanjing University, Nanjing 210093, China.
  • 2 the Jiangsu Provincial Center for Disease Control and Prevention, Nanjing 210009, China.
  • 3 the National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China, and.
  • 4 the Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, Twin Cities, St. Paul, Minnesota 55108.
  • 5 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 [email protected] [email protected].
PMID: 27226560 DOI: 10.1074/jbc.M116.715599
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.

Keywords

lipid droplet; negative-strand RNA virus; protein-protein interaction; viral protein; viral replication.

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