title: A network of protein interactions around the herpes simplex virus tegument protein VP22.
abstract: Assembly of the herpesvirus tegument is poorly understood but is believed to involve interactions between outer tegument proteins and the cytoplasmic domains of envelope glycoproteins. Here, we present the detailed characterization of a multicomponent glycoprotein-tegument complex found in herpes simplex virus 1 (HSV-1)-infected cells. We demonstrate that the tegument protein VP22 bridges a complex between glycoprotein E (gE) and glycoprotein M (gM). Glycoprotein I (gI), the known binding partner of gE, is also recruited into this gE-VP22-gM complex but is not required for its formation. Exclusion of the glycoproteins gB and gD and VP22's major binding partner VP16 demonstrates that recruitment of virion components into this complex is highly selective. The immediate-early protein ICP0, which requires VP22 for packaging into the virion, is also assembled into this gE-VP22-gM-gI complex in a VP22-dependent fashion. Although subcomplexes containing VP22 and ICP0 can be formed when either gE or gM are absent, optimal complex formation requires both glycoproteins. Furthermore, and in line with complex formation, neither of these glycoproteins is individually required for VP22 or ICP0 packaging into the virion, but deletion of gE and gM greatly reduces assembly of both VP22 and ICP0. Double deletion of gE and gM also results in small plaque size, reduced virus yield, and defective secondary envelopment, similar to the phenotype previously shown for pseudorabies virus. Hence, we suggest that optimal gE-VP22-gM-gI-ICP0 complex formation correlates with efficient virus morphogenesis and spread. These data give novel insights into the poorly understood process of tegument acquisition.
authors.affiliation: Section of Virology, Faculty of Medicine, Imperial College London, London, United Kingdom.
authors.forename: Kevin
authors.initials: K
authors.lastname: Maringer
authors.forename: Julianna
authors.initials: J
authors.lastname: Stylianou
authors.forename: Gillian
authors.initials: G
authors.lastname: Elliott
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002522:Chlorocebus aethiops; D018259:Herpesvirus 1, Human / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D017874:Immediate-Early Proteins / Q000378:metabolism; D047468:Immunoprecipitation; D046529:Microscopy, Electron, Transmission; D046912:Multiprotein Complexes / Q000378:metabolism*; D025941:Protein Interaction Mapping; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000378:metabolism; D015678:Viral Structural Proteins / Q000378:metabolism*; D014779:Virus Replication / Q000502:physiology*
chemical_list: D017874:Immediate-Early Proteins; D046912:Multiprotein Complexes; D014759:Viral Envelope Proteins; D015678:Viral Structural Proteins; C073413:herpes simplex virus type 1 protein VP22