title: Herpes simplex virus type 1 UL14 tegument protein regulates intracellular compartmentalization of major tegument protein VP16.
abstract: BACKGROUND
  Herpes simplex virus type 1 (HSV-1) has a complicated life-cycle, and its genome encodes many components that can modify the cellular environment to facilitate efficient viral replication. The protein UL14 is likely involved in viral maturation and egress (Cunningham C. et al), and it facilitates the nuclear translocation of viral capsids and the tegument protein VP16 during the immediate-early phase of infection (Yamauchi Y. et al, 2008). UL14 of herpes simplex virus type 2 exhibits multiple functions (Yamauchi Y. et al, 2001, 2002, 2003).
  
  
  METHODS
  To better understand the function(s) of UL14, we generated VP16-GFP-incorporated UL14-mutant viruses with either single (K51M) or triple (R60A, R64A, E68D) amino acid substitutions in the heat shock protein (HSP)-like sequence of UL14. We observed the morphology of cells infected with UL14-null virus and amino acid-substituted UL14-mutant viruses at different time points after infection.
  
  
  RESULTS
  UL14(3P)-VP16GFP and UL14D-VP16GFP (UL14-null) viruses caused similar defects with respect to growth kinetics, compartmentalization of tegument proteins, and cellular morphology in the late phase. Both the UL14D-VP16GFP and UL14(3P)-VP16GFP viruses led to the formation of an aggresome that incorporated some tegument proteins but did not include nuclear-egressed viral capsids.
  
  
  CONCLUSIONS
  Our findings suggest that a cluster of charged residues within the HSP-like sequence of UL14 is important for the molecular chaperone-like functions of UL14, and this activity is required for the acquisition of functionality of VP16 and UL46. In addition, UL14 likely contributes to maintaining cellular homeostasis following infection, including cytoskeletal organization. However, direct interactions between UL14 and VP16, UL46, or other cellular or viral proteins remain unclear.
authors.affiliation: Department of Virology, Graduate School of Medicine, Nagoya University, Tsurumai-cho 65, Showa-ku, Nagoya 466-8550, Japan.
authors.forename: Akane
authors.initials: A
authors.lastname: Ohta
authors.forename: Yohei
authors.initials: Y
authors.lastname: Yamauchi
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Muto
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kimura
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Nishiyama
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D000956:Antigens, Viral / Q000378:metabolism; D002460:Cell Line; D002522:Chlorocebus aethiops; D003599:Cytoskeleton / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000821:virology; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D017405:Herpes Simplex Virus Protein Vmw65 / Q000235:genetics / Q000378:metabolism*; D018259:Herpesvirus 1, Human / Q000254:growth & development / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D008969:Molecular Sequence Data; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D011817:Rabbits; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014764:Viral Proteins / Q000378:metabolism*
chemical_list: D000956:Antigens, Viral; D017405:Herpes Simplex Virus Protein Vmw65; D050505:Mutant Proteins; D011993:Recombinant Fusion Proteins; C402639:UL14 protein, Human herpesvirus 1; C414831:UL46 protein, Human herpesvirus 1; D014764:Viral Proteins; D049452:Green Fluorescent Proteins