title: Tetherin restricts HSV-2 release and is counteracted by multiple viral glycoproteins.
abstract: Tetherin has been defined as a restriction factor of HIV-1 and several other enveloped viruses. However, the significance of tetherin in viral infection remains to be further addressed. Here, we investigated whether tetherin plays a role in HSV-2 infection. Our study revealed that overexpression of tetherin restricted the release of HSV-2 into the extracellular medium, while knockdown of tetherin by siRNA enhanced its release. We further demonstrated that HSV-2 infection and viral glycoproteins gB, gD, gH and gL but not gM significantly downregulated the endogenous expression of tetherin. Additional study indicated that tetherin likely physically interacted with gB, gD, gH and gL. This is the first time that tetherin has been shown to be counteracted by multiple viral components of a virus. Our findings inform the complexity of HSV-2-host interactions, providing basis for understanding the role of tetherin as a viral restriction factor and the mechanisms underlying viral countermeasures.
authors.affiliation: State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China.
authors.forename: Yalan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China; University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Sukun
authors.initials: S
authors.lastname: Luo
authors.affiliation: State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China; University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Siyi
authors.initials: S
authors.lastname: He
authors.affiliation: State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China; University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Mudan
authors.initials: M
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China; University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China; University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Chang
authors.initials: C
authors.lastname: Li
authors.affiliation: State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China.
authors.forename: Wenjie
authors.initials: W
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China; University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Bodan
authors.initials: B
authors.lastname: Hu
authors.affiliation: Institute for Infection and Immunity, St George's University of London, London SW17 0RE, UK.
authors.forename: George E
authors.initials: GE
authors.lastname: Griffin
authors.affiliation: Section of Infectious Diseases, Faculty of Medicine, Imperial College London, St. Mary's Campus, London W2 1PG, UK.
authors.forename: Robin J
authors.initials: RJ
authors.lastname: Shattock
authors.affiliation: State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China; Institute for Infection and Immunity, St George's University of London, London SW17 0RE, UK. Electronic address: qhu@wh.iov.cn.
authors.forename: Qinxue
authors.initials: Q
authors.lastname: Hu
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D058851:GPI-Linked Proteins / Q000235:genetics / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D018258:Herpesvirus 2, Human / Q000502:physiology*; D006801:Humans; D016133:Polymerase Chain Reaction / Q000379:methods; D034622:RNA Interference; D053586:Virus Internalization; D057074:Virus Release; D000074010:Bone Marrow Stromal Antigen 2
chemical_list: D015703:Antigens, CD; D058851:GPI-Linked Proteins; D006023:Glycoproteins; C094572:BST2 protein, human; D000074010:Bone Marrow Stromal Antigen 2
keywords: HSV-2; Tetherin; Viral glycoprotein; Viral release