title: Herpes Simplex Virus 1 Induces Phosphorylation and Reorganization of Lamin A/C through the γ134.5 Protein That Facilitates Nuclear Egress.
abstract: Herpes simplex virus 1 (HSV-1) remodels nuclear membranes during virus egress. Although the UL31 and UL34 proteins control nucleocapsid transit in infected cells, the molecular interactions required for their function are unclear. Here we report that the γ134.5 gene product of HSV-1 facilitates nucleocapsid release to the cytoplasm through bridging the UL31/UL34 complex, cellular p32, and protein kinase C. Unlike wild-type virus, an HSV mutant devoid of γ134.5 or its amino terminus is crippled for viral growth and release. This is attributable to a defect in virus nuclear egress. In infected cells, wild-type virus recruits protein kinase C to the nuclear membrane and triggers its activation, whereas the γ134.5 mutants fail to exert such an effect. Accordingly, the γ134.5 mutants are unable to induce phosphorylation and reorganization of lamin A/C. When expressed in host cells γ134.5 targets p32 and protein kinase C. Meanwhile, it communicates with the UL31/UL34 complex through UL31. Deletion of the amino terminus from γ134.5 disrupts its activity. These results suggest that disintegration of the nuclear lamina mediated by γ134.5 promotes HSV replication.
  
  
  OBJECTIVE
  HSV nuclear egress is a key step that determines the outcome of viral infection. While the nuclear egress complex mediates capsid transit across the nuclear membrane, the regulatory components are not clearly defined in virus-infected cells. We report that the γ134.5 gene product, a virulence factor of HSV-1, facilitates nuclear egress cooperatively with cellular p32, protein kinase C, and the nuclear egress complex. This work highlights a viral mechanism that may contribute to the pathogenesis of HSV infection.
authors.affiliation: Department of Microbiology and Immunology, College of Medicine, University of Illinois, Chicago, Illinois, USA.|Department of Biochemistry, College of Life Sciences, Nankai University, Tianjin, People's Republic of China.
authors.forename: Songfang
authors.initials: S
authors.lastname: Wu
authors.affiliation: Department of Biochemistry, College of Life Sciences, Nankai University, Tianjin, People's Republic of China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Pan
authors.affiliation: Department of Biochemistry, College of Life Sciences, Nankai University, Tianjin, People's Republic of China.
authors.forename: Liming
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Pathobiological Sciences, Louisiana State University, Baton Rouge, Louisiana, USA.
authors.forename: Joel
authors.initials: J
authors.lastname: Baines
authors.affiliation: Department of Microbiology, University of Iowa, Iowa City, Iowa, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Roller
authors.affiliation: Department of Microbiology and Immunology, College of Medicine, University of Illinois, Chicago, Illinois, USA.
authors.forename: Joshua
authors.initials: J
authors.lastname: Ames
authors.affiliation: Department of Biochemistry, College of Life Sciences, Nankai University, Tianjin, People's Republic of China.
authors.forename: Mengmeng
authors.initials: M
authors.lastname: Yang
authors.affiliation: Department of Biochemistry, College of Life Sciences, Nankai University, Tianjin, People's Republic of China.
authors.forename: Jiyan
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Biochemistry, College of Life Sciences, Nankai University, Tianjin, People's Republic of China.
authors.forename: Da
authors.initials: D
authors.lastname: Chen
authors.affiliation: Department of Biochemistry, College of Life Sciences, Nankai University, Tianjin, People's Republic of China.
authors.forename: Yaohui
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Biochemistry, College of Life Sciences, Nankai University, Tianjin, People's Republic of China.
authors.forename: Cuizhu
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry, College of Life Sciences, Nankai University, Tianjin, People's Republic of China tshuo@uic.edu caoyj@nankai.edu.cn.
authors.forename: Youjia
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Department of Microbiology and Immunology, College of Medicine, University of Illinois, Chicago, Illinois, USA tshuo@uic.edu caoyj@nankai.edu.cn.
authors.forename: Bin
authors.initials: B
authors.lastname: He
mesh_terms: D000818:Animals; D002213:Capsid / Q000378:metabolism; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism / Q000821:virology; D002522:Chlorocebus aethiops; D003593:Cytoplasm / Q000378:metabolism / Q000821:virology; D006367:HeLa Cells; D018259:Herpesvirus 1, Human / Q000378:metabolism*; D006801:Humans; D034904:Lamin Type A / Q000378:metabolism*; D009685:Nuclear Envelope / Q000378:metabolism / Q000821:virology; D034881:Nuclear Lamina / Q000378:metabolism / Q000821:virology; D009687:Nuclear Proteins / Q000378:metabolism; D019251:Nucleocapsid / Q000378:metabolism; D010766:Phosphorylation / Q000502:physiology*; D011493:Protein Kinase C / Q000378:metabolism; D014709:Vero Cells; D014764:Viral Proteins / Q000378:metabolism*; D019065:Virus Assembly / Q000502:physiology; D057074:Virus Release / Q000502:physiology*
chemical_list: D034904:Lamin Type A; D009687:Nuclear Proteins; D014764:Viral Proteins; C440308:lamin C; D011493:Protein Kinase C