Activation of H2AX and ATM in varicella-zoster virus (VZV)-infected cells is associated with expression of specific VZV genes

Virology. 2014 Mar:452-453:52-8. doi: 10.1016/j.virol.2013.12.039. Epub 2014 Jan 29.

Abstract

Mammalian cells activate DNA damage response pathways in response to virus infections. Activation of these pathways can enhance replication of many viruses, including herpesviruses. Activation of cellular ATM results in phosphorylation of H2AX and recruits proteins to sites of DNA damage. We found that varicella-zoster (VZV) infected cells had elevated levels of phosphorylated H2AX and phosphorylated ATM and that these levels increased in cells infected with VZV deleted for ORF61 or ORF63, but not deleted for ORF67. Expression of VZV ORF61, ORF62, or ORF63 alone did not result in phosphorylation of H2AX. While BGLF4, the Epstein-Barr virus homolog of VZV ORF47 protein kinase, phosphorylates H2AX and ATM, neither VZV ORF47 nor ORF66 protein kinase phosphorylated H2AX or ATM. Cells lacking ATM had no reduction in VZV replication. Thus, VZV induces phosphorylation of H2AX and ATM and this effect is associated with the presence of specific VZV genes in virus-infected cells.

Keywords: ATM; DNA damage; H2AX; Herpes simplex virus; Herpesvirus; Varicella-zoster virus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Ataxia Telangiectasia Mutated Proteins / genetics
  • Ataxia Telangiectasia Mutated Proteins / metabolism*
  • Gene Deletion
  • Gene Expression Regulation, Viral
  • Herpes Zoster / enzymology
  • Herpes Zoster / genetics
  • Herpes Zoster / metabolism*
  • Herpes Zoster / virology
  • Herpesvirus 3, Human / genetics*
  • Herpesvirus 3, Human / metabolism
  • Histones / genetics
  • Histones / metabolism*
  • Humans
  • Immediate-Early Proteins / genetics
  • Immediate-Early Proteins / metabolism*
  • Phosphorylation
  • Viral Envelope Proteins / genetics
  • Viral Envelope Proteins / metabolism*
  • Viral Proteins / genetics
  • Viral Proteins / metabolism*

Substances

  • H2AX protein, human
  • Histones
  • Immediate-Early Proteins
  • Viral Envelope Proteins
  • Viral Proteins
  • glycoprotein IV, varicella-zoster virus
  • immediate early protein 63, Human herpesvirus 3
  • protein 61, Varicella-zoster virus
  • ATM protein, human
  • Ataxia Telangiectasia Mutated Proteins