Analysis of Cyclin-Dependent Kinase Activity After Herpes Simplex Virus Type 2 Infection

J Gen Virol. 1997 Dec;78 ( Pt 12):3341-8. doi: 10.1099/0022-1317-78-12-3341.

Abstract

Small DNA viruses (adenoviruses, simian virus 40, or human papillomaviruses) induce S-phase progression but prevent cell division to provide precursors for viral DNA replication. Herpes simplex viruses types 1 or 2 (HSV-1 or HSV-2) contain genes which encode DNA-metabolizing enzymes, for example, ribonucleotide reductase, thymidine kinase and dUTPase, suggesting that S-phase factors are not required for an efficient infection. However, several studies indicated that HSV induces some events that occur during cell-cycle progression. To determine if HSV-2 induces S-phase entry, we examined serum-arrested African green monkey kidney cells (CV-1) after infection. Two hours after infection steady-state levels of the S-phase-specific cyclin, cyclin A, increased. S-phase cyclin-dependent kinase activity (CDK2) was stimulated 10-fold 8 h after infection but decreased at 16 or 24 h after infection. Mitotic CDK activity (CDC2) was not activated after infection, in part due to decreases in CDC2 protein levels and inactivation of enzymatic activity resulting from tyrosine phosphorylation of CDC2. Furthermore, CDK4 activity was not dramatically affected by infection. These studies indicate that HSV-2 infection selectively activates CDK2 after infection but cell-cycle progression does not occur. We hypothesize that infection activates certain components of the cell cycle which enhance viral gene expression and DNA replication.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • CDC2-CDC28 Kinases*
  • Cell Cycle
  • Cell Line
  • Cyclin-Dependent Kinase 2
  • Cyclin-Dependent Kinase 4
  • Cyclin-Dependent Kinases / metabolism*
  • Gene Expression Regulation, Viral
  • Haplorhini
  • Herpes Genitalis / enzymology*
  • Herpesvirus 2, Human*
  • Humans
  • Protein-Serine-Threonine Kinases / metabolism*
  • Proto-Oncogene Proteins*

Substances

  • Proto-Oncogene Proteins
  • Protein-Serine-Threonine Kinases
  • CDC2-CDC28 Kinases
  • CDK2 protein, human
  • CDK4 protein, human
  • Cyclin-Dependent Kinase 2
  • Cyclin-Dependent Kinase 4
  • Cyclin-Dependent Kinases