title: HSV-1 nucleocapsid egress mediated by UL31 in association with UL34 is impeded by cellular transmembrane protein 140.
abstract: During HSV-1 infection, the viral UL31 protein forms a complex with the UL34 protein at the cellular nuclear membrane, where both proteins play important roles in the envelopment of viral nucleocapsids and their egress into the cytoplasm. To characterize the mechanism of HSV-1 nucleocapsid egress, we screened host proteins to identify proteins that interacted with UL31 via yeast two-hybrid analysis. Transmembrane protein 140 (TMEM140), was identified and confirmed to bind to and co-localize with UL31 during viral infection. Further studies indicated that TMEM140 inhibits HSV-1 proliferation through selectively blocking viral nucleocapsid egress during the viral assembly process. The blockage function of TMEM140 is mediated by impeding the formation of the UL31-UL34 complex due to competitive binding to UL31. Collectively, these data suggest the essentiality of the UL31-UL34 interaction in the viral nucleocapsid egress process and provide a new anti-HSV-1 strategy in viral assembly process of nucleocapsid egress.
authors.affiliation: Department of Viral Immunology, Institute of Medical Biology, Chinese Academy of Medicine Science, Peking Union Medical College, Kunming 650118, PR China; Yunnan Academy of Tobacco Science, Kunming, Yunnan 650106, PR China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Guan
authors.affiliation: Department of Viral Immunology, Institute of Medical Biology, Chinese Academy of Medicine Science, Peking Union Medical College, Kunming 650118, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Guo
authors.affiliation: Department of Viral Immunology, Institute of Medical Biology, Chinese Academy of Medicine Science, Peking Union Medical College, Kunming 650118, PR China.
authors.forename: Erxia
authors.initials: E
authors.lastname: Yang
authors.affiliation: Department of Viral Immunology, Institute of Medical Biology, Chinese Academy of Medicine Science, Peking Union Medical College, Kunming 650118, PR China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Liao
authors.affiliation: Department of Viral Immunology, Institute of Medical Biology, Chinese Academy of Medicine Science, Peking Union Medical College, Kunming 650118, PR China.
authors.forename: Longding
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Viral Immunology, Institute of Medical Biology, Chinese Academy of Medicine Science, Peking Union Medical College, Kunming 650118, PR China.
authors.forename: Yanchun
authors.initials: Y
authors.lastname: Che
authors.affiliation: Department of Viral Immunology, Institute of Medical Biology, Chinese Academy of Medicine Science, Peking Union Medical College, Kunming 650118, PR China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Viral Immunology, Institute of Medical Biology, Chinese Academy of Medicine Science, Peking Union Medical College, Kunming 650118, PR China.
authors.forename: Lichun
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Viral Immunology, Institute of Medical Biology, Chinese Academy of Medicine Science, Peking Union Medical College, Kunming 650118, PR China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Viral Immunology, Institute of Medical Biology, Chinese Academy of Medicine Science, Peking Union Medical College, Kunming 650118, PR China. Electronic address: imbcams.lq@gmail.com.
authors.forename: Qihan
authors.initials: Q
authors.lastname: Li
mesh_terms: D000595:Amino Acid Sequence; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D006561:Herpes Simplex / Q000235:genetics / Q000378:metabolism* / Q000821:virology*; D018259:Herpesvirus 1, Human / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D019251:Nucleocapsid / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D016415:Sequence Alignment; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D019065:Virus Assembly; D057074:Virus Release
chemical_list: D002352:Carrier Proteins; D008565:Membrane Proteins; D009687:Nuclear Proteins; C000594307:TMEM140 protein, human; C108721:UL31 protein, Human herpesvirus 1; C403420:UL34 protein, Human herpesvirus 1; D014764:Viral Proteins
keywords: Herpes simplex virus 1 (HSV-1); Nucleocapsid egress; Transmembrane protein 140 (TMEM140); UL31; UL34