Hypoxia can contribute to the induction of the Epstein-Barr virus (EBV) lytic cycle

J Clin Virol. 2006 Oct;37(2):98-103. doi: 10.1016/j.jcv.2006.06.013. Epub 2006 Aug 22.

Abstract

Background: Like other herpes viruses, latent Epstein-Barr virus (EBV) infection can be reactivated to lytic replication. Reactivation can be achieved by treatment with various reagents, including tetradecanoyl phorbol acetate (TPA) and Ca2+ ionophores. Relatively little is known about the physiological factors related to reactivation of EBV. Previous studies have demonstrated that G0/G1 cell cycle arrest is associated with EBV activation, and that hypoxic conditions can induce cell cycle arrest. In the present study we investigated the effect of hypoxia on reactivation of EBV.

Objective and methods: Hypoxic culture conditions were established and the expression of Zta protein and the number of EBV DNA copies were measured in B95-8 cells maintained under these conditions.

Results: Hypoxia treatment not only increased the expression of the EBV immediate-early protein Zta (which mediates the switch between the latent and lytic form of infection), but also increased the number of EBV DNA copies in B95-8 cells.

Conclusions: EBV in latent infection can be activated to lytic infection by hypoxia treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Callithrix
  • Cell Cycle
  • Cell Hypoxia*
  • DNA-Binding Proteins / genetics
  • Gene Dosage
  • Genes, Immediate-Early
  • Herpesvirus 4, Human / physiology*
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics
  • Promoter Regions, Genetic
  • Trans-Activators / genetics
  • Viral Proteins / genetics

Substances

  • BZLF1 protein, Herpesvirus 4, Human
  • DNA-Binding Proteins
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Trans-Activators
  • Viral Proteins