Hyperphosphorylation of histone deacetylase 2 by alphaherpesvirus US3 kinases. Academic Article uri icon

Overview

MeSH

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Cell Line
  • Cercopithecus aethiops
  • DNA Primers
  • Genes, Viral
  • Herpesvirus 1, Human
  • Herpesvirus 1, Suid
  • Herpesvirus 3, Human
  • Humans
  • Molecular Sequence Data
  • Mutation
  • Phosphorylation
  • Sequence Homology, Amino Acid
  • Vero Cells

MeSH Major

  • Alphaherpesvirinae
  • Histone Deacetylase 2
  • Protein-Serine-Threonine Kinases
  • Viral Proteins

abstract

  • A serine/threonine (S/T) kinase encoded by the US3 gene of herpes simplex virus type 1 (HSV-1) is conserved in varicella-zoster virus (VZV) and pseudorabies virus (PRV). Expression of US3 kinase in cells transformed with US3 expression plasmids or infected with each virus results in hyperphosphorylation of histone deacetylase 2 (HDAC2). Mapping studies revealed that each US3 kinase phosphorylates HDAC2 at the same unique conserved Ser residue in its C terminus. HDAC2 was also hyperphosphorylated in cells infected with PRV lacking US3 kinase, indicating that hyperphosphorylation of HDAC2 by PRV occurs in a US3-independent manner. Specific chemical inhibition of class I HDAC activity increases the plaquing efficiency of VZV and PRV lacking US3 or its enzymatic activity, whereas only minimal effects are observed with wild-type viruses, suggesting that VZV and PRV US3 kinase activities target HDACs to reduce viral genome silencing and allow efficient viral replication. However, no effect was observed for wild-type or US3 null HSV-1. Thus, we have demonstrated that while HDAC2 is a conserved target of alphaherpesvirus US3 kinases, the functional significance of these events is virus specific.

publication date

  • October 2010

has subject area

  • Alphaherpesvirinae
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Cell Line
  • Cercopithecus aethiops
  • DNA Primers
  • Genes, Viral
  • Herpesvirus 1, Human
  • Herpesvirus 1, Suid
  • Herpesvirus 3, Human
  • Histone Deacetylase 2
  • Humans
  • Molecular Sequence Data
  • Mutation
  • Phosphorylation
  • Protein-Serine-Threonine Kinases
  • Sequence Homology, Amino Acid
  • Vero Cells
  • Viral Proteins

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC2937806

Digital Object Identifier (DOI)

  • 10.1128/JVI.00981-10

PubMed ID

  • 20660201

Additional Document Info

start page

  • 9666

end page

  • 9676

volume

  • 84

number

  • 19