Stress up-regulates neuronal expression of the herpes simplex virus type 2 large subunit of ribonucleotide reductase (R1; ICP10) by activating activator protein 1

J Neurovirol. 2005 Aug;11(4):329-36. doi: 10.1080/13550280591002423.

Abstract

Herpes simplex virus type 2 (HSV-2) genes expressed in neuronal cells in response to stress stimuli that trigger latency reactivation are largely unknown. Using a chloramphenicol acetyltransferase (CAT) reporter assay we found that stress caused a significant (P < .001) increase in ICP10 expression in neuronal cells. Up-regulation correlated with activator protein (AP)-1 activation, notably c-Jun and c-Fos that bind cognate elements in the ICP10 promoter. It was blocked by mutation of the AP-1 motifs in the ICP10 promoter. ICP10 expression protected neuronal cells from stress-induced apoptosis. The data suggest that ICP10 may contribute to HSV-2 reactivation by increasing neuronal survival.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Survival
  • Gene Expression Regulation, Viral
  • Genes, Reporter
  • Heat-Shock Response
  • Herpes Genitalis / virology*
  • Herpesvirus 2, Human / genetics*
  • Herpesvirus 2, Human / growth & development
  • Molecular Sequence Data
  • Neurons / cytology
  • Neurons / physiology
  • Neurons / virology*
  • PC12 Cells
  • Promoter Regions, Genetic / physiology
  • Protein Serine-Threonine Kinases / genetics*
  • Rats
  • Ribonucleotide Reductases / genetics*
  • Transcription Factor AP-1 / metabolism*
  • Up-Regulation

Substances

  • Transcription Factor AP-1
  • ICP10 protein, herpes simplex virus type 2
  • Ribonucleotide Reductases
  • Protein Serine-Threonine Kinases