title: Varicella-zoster virus glycoprotein M homolog is glycosylated, is expressed on the viral envelope, and functions in virus cell-to-cell spread.
abstract: Although envelope glycoprotein M (gM) is highly conserved among herpesviruses, the varicella-zoster virus (VZV) gM homolog has never been investigated. Here we characterized the VZV gM homolog and analyzed its function in VZV-infected cells. The VZV gM homolog was expressed on virions as a glycoprotein modified with a complex N-linked oligosaccharide and localized mainly to the Golgi apparatus and the trans-Golgi network in infected cells. To analyze its function, a gM deletion mutant was generated using the bacterial artificial chromosome system in Escherichia coli, and the virus was reconstituted in MRC-5 cells. VZV is highly cell associated, and infection proceeds mostly by cell-to-cell spread. Compared with wild-type VZV, the gM deletion mutant showed a 90% reduction in plaque size and 50% of the cell-to-cell spread in MRC-5 cells. The analysis of infected cells by electron microscopy revealed numerous aberrant vacuoles containing electron-dense materials in cells infected with the deletion mutant virus but not in those infected with wild-type virus. However, enveloped immature particles termed L particles were found at the same level on the surfaces of cells infected with either type of virus, indicating that envelopment without a capsid might not be impaired. These results showed that VZV gM is important for efficient cell-to-cell virus spread in cell culture, although it is not essential for virus growth.
authors.affiliation: Laboratory of Virology and Vaccinology, Division of Biomedical Research, National Institute of Biomedical Innovation, 7-6-8, Saito-Asagi, Ibaraki, Osaka 567-0085, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Yamagishi
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Sadaoka
authors.forename: Hironori
authors.initials: H
authors.lastname: Yoshii
authors.forename: Pranee
authors.initials: P
authors.lastname: Somboonthum
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Imazawa
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Nagaike
authors.forename: Keiichi
authors.initials: K
authors.lastname: Ozono
authors.forename: Koichi
authors.initials: K
authors.lastname: Yamanishi
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Mori
mesh_terms: D002460:Cell Line; D003593:Cytoplasm / Q000648:ultrastructure; D017353:Gene Deletion; D006023:Glycoproteins / Q000032:analysis / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D006031:Glycosylation; D006056:Golgi Apparatus / Q000737:chemistry; D014645:Herpesvirus 3, Human / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D006801:Humans; D046529:Microscopy, Electron, Transmission; D014617:Vacuoles / Q000648:ultrastructure; D010948:Viral Plaque Assay; D014764:Viral Proteins / Q000032:analysis / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D014771:Virion / Q000737:chemistry
chemical_list: D006023:Glycoproteins; D014764:Viral Proteins