title: HSV-2 glycoprotein gD targets the CC domain of tetherin and promotes tetherin degradation via lysosomal pathway.
abstract: HSV-2 is the major cause of genital herpes. We previously demonstrated that the host viral restriction factor tetherin restricts HSV-2 release and is antagonized by several HSV-2 glycoproteins. However, the mechanisms underlying HSV-2 glycoproteins mediated counteraction of tetherin remain unclear. In this study, we investigated whether tetherin restricts the cell-to-cell spread of HSV-2 and the mechanisms underlying HSV-2 gD mediated antagonism of tetherin.
  
  
  
  Infectious center assays were used to test whether tetherin could affect cell-to-cell spread of HSV-2. Coimmunoprecipitation assays were performed to map the tetherin domains required for HSV-2 gD-mediated downregulation. Immunoflurence assays were performed to detect the accumulation of tetherin in lysosomes or proteasomes. All experiments were repeated for at least three times and the data were performed statistical analysis.
  
  
  
  1) Tetherin restricts cell-to-cell spread of HSV-2; 2) HSV-2 gD specifically interacts with the CC domain of tetherin; 3) HSV-2 gD promotes tetherin to the lysosomal degradation pathway.
  
  
  
  Tetherin not only restricts HSV-2 release but also its cell-to-cell spread. In turn, HSV-2 gD targets the CC domain of tetherin and promotes its degradation in the lysosome. Findings in this study have increased our understanding of tetherin restriction and viral countermeasures.
authors.affiliation: State Key Laboratory of Virology, Chinese Academy of Sciences, Wuhan Institute of Virology, Wuhan, 430071, China. liuyl@wh.iov.cn.
authors.forename: Yalan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Virology, Chinese Academy of Sciences, Wuhan Institute of Virology, Wuhan, 430071, China.|University of Chinese Academy of Sciences, Beijing, 100049, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Li
authors.affiliation: State Key Laboratory of Virology, Chinese Academy of Sciences, Wuhan Institute of Virology, Wuhan, 430071, China.|University of Chinese Academy of Sciences, Beijing, 100049, China.
authors.forename: Di
authors.initials: D
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Virology, Chinese Academy of Sciences, Wuhan Institute of Virology, Wuhan, 430071, China.
authors.forename: Mudan
authors.initials: M
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Virology, Chinese Academy of Sciences, Wuhan Institute of Virology, Wuhan, 430071, China.|Institute for Infection and Immunity, St George's University of London, London, SW17 0RE, UK.
authors.forename: Qinxue
authors.initials: Q
authors.lastname: Hu
mesh_terms: D015703:Antigens, CD / Q000378:metabolism*; D002460:Cell Line; D004847:Epithelial Cells / Q000502:physiology / Q000821:virology; D058851:GPI-Linked Proteins / Q000378:metabolism; D018258:Herpesvirus 2, Human / Q000254:growth & development* / Q000276:immunology; D054884:Host-Pathogen Interactions; D006801:Humans; D057131:Immune Evasion; D047468:Immunoprecipitation; D008856:Microscopy, Fluorescence; D011485:Protein Binding; D025941:Protein Interaction Mapping; D059748:Proteolysis; D014759:Viral Envelope Proteins / Q000378:metabolism*; D057074:Virus Release; D000074010:Bone Marrow Stromal Antigen 2
chemical_list: D015703:Antigens, CD; D058851:GPI-Linked Proteins; D014759:Viral Envelope Proteins; C094572:BST2 protein, human; D000074010:Bone Marrow Stromal Antigen 2; C040570:glycoprotein D-herpes simplex virus type 2
keywords: HSV-2 glycoprotein D; Interaction; Lysosomal degradation; Tetherin