title: Dual Function of the pUL7-pUL51 Tegument Protein Complex in Herpes Simplex Virus 1 Infection.
abstract: The tegument of herpesviruses is a highly complex structural layer between the nucleocapsid and the envelope of virions. Tegument proteins play both structural and regulatory functions during replication and spread, but the interactions and functions of many of these proteins are poorly understood. Here we focus on two tegument proteins from herpes simplex virus 1 (HSV-1), pUL7 and pUL51, which have homologues in all other herpesviruses. We have now identified that HSV-1 pUL7 and pUL51 form a stable and direct protein-protein interaction, their expression levels rely on the presence of each other, and they function as a complex in infected cells. We demonstrate that expression of the pUL7-pUL51 complex is important for efficient HSV-1 assembly and plaque formation. Furthermore, we also discovered that the pUL7-pUL51 complex localizes to focal adhesions at the plasma membrane in both infected cells and in the absence of other viral proteins. The expression of pUL7-pUL51 is important to stabilize focal adhesions and maintain cell morphology in infected cells and cells infected with viruses lacking pUL7 and/or pUL51 round up more rapidly than cells infected with wild-type HSV-1. Our data suggest that, in addition to the previously reported functions in virus assembly and spread for pUL51, the pUL7-pUL51 complex is important for maintaining the attachment of infected cells to their surroundings through modulating the activity of focal adhesion complexes.
  
  
  OBJECTIVE
  Herpesviridae is a large family of highly successful human and animal pathogens. Virions of these viruses are composed of many different proteins, most of which are contained within the tegument, a complex structural layer between the nucleocapsid and the envelope within virus particles. Tegument proteins have important roles in assembling virus particles as well as modifying host cells to promote virus replication and spread. However, little is known about the function of many tegument proteins during virus replication. Our study focuses on two tegument proteins from herpes simplex virus 1 that are conserved in all herpesviruses: pUL7 and pUL51. We demonstrate that these proteins directly interact and form a functional complex that is important for both virus assembly and modulation of host cell morphology. Further, we identify for the first time that these conserved herpesvirus tegument proteins localize to focal adhesions in addition to cytoplasmic juxtanuclear membranes within infected cells.
authors.affiliation: Division of Virology, Department of Pathology, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Anna
authors.initials: A
authors.lastname: Albecka
authors.affiliation: Division of Virology, Department of Pathology, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Danielle J
authors.initials: DJ
authors.lastname: Owen
authors.affiliation: Division of Virology, Department of Pathology, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Lyudmila
authors.initials: L
authors.lastname: Ivanova
authors.affiliation: Division of Virology, Department of Pathology, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Juliane
authors.initials: J
authors.lastname: Brun
authors.affiliation: Division of Virology, Department of Pathology, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Rukayya
authors.initials: R
authors.lastname: Liman
authors.affiliation: Division of Virology, Department of Pathology, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Laura
authors.initials: L
authors.lastname: Davies
authors.affiliation: Division of Virology, Department of Pathology, University of Cambridge, Cambridge, United Kingdom.
authors.forename: M Firoz
authors.initials: MF
authors.lastname: Ahmed
authors.affiliation: Division of Virology, Department of Pathology, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Susanna
authors.initials: S
authors.lastname: Colaco
authors.affiliation: Division of Virology, Department of Pathology, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Michael
authors.initials: M
authors.lastname: Hollinshead
authors.affiliation: Division of Virology, Department of Pathology, University of Cambridge, Cambridge, United Kingdom scg34@cam.ac.uk cmc56@cam.ac.uk.
authors.forename: Stephen C
authors.identifier: http://orcid.org/0000-0003-4547-4034
authors.initials: SC
authors.lastname: Graham
authors.affiliation: Division of Virology, Department of Pathology, University of Cambridge, Cambridge, United Kingdom scg34@cam.ac.uk cmc56@cam.ac.uk.
authors.forename: Colin M
authors.identifier: http://orcid.org/0000-0001-9918-9998
authors.initials: CM
authors.lastname: Crump
mesh_terms: D000818:Animals; D002522:Chlorocebus aethiops; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism*; D019915:DNA Primase / Q000235:genetics / Q000378:metabolism*; D015967:Gene Expression Regulation, Viral; D057809:HEK293 Cells; D006561:Herpes Simplex / Q000378:metabolism* / Q000821:virology*; D018259:Herpesvirus 1, Human / Q000502:physiology* / Q000648:ultrastructure; D006801:Humans; D046912:Multiprotein Complexes / Q000378:metabolism*; D011485:Protein Binding; D021381:Protein Transport; D014709:Vero Cells; D014763:Viral Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*; D019065:Virus Assembly
chemical_list: D046912:Multiprotein Complexes; C000597859:UL7 protein, human herpesvirus 1; D014763:Viral Matrix Proteins; D014764:Viral Proteins; D019915:DNA Primase; C062021:helicase-primase, Human herpesvirus 1; D004265:DNA Helicases
keywords: UL51; UL7; focal adhesion; herpes simplex virus; human herpesviruses; tegument