Ectopic expression of HCMV IE72 and IE86 proteins is sufficient to induce early gene expression but not production of infectious virus in undifferentiated promonocytic THP-1 cells

Virology. 2007 Jun 20;363(1):174-88. doi: 10.1016/j.virol.2007.01.036. Epub 2007 Feb 27.

Abstract

Human cytomegalovirus (HCMV) reactivation from latency causes disease in individuals who are immunocompromised or immunosuppressed. Activation of the major immediate-early (MIE) promoter is thought to be an initial step for reactivation. We determined whether expression of the MIE gene products in trans was sufficient to circumvent an HCMV latent-like state in an undifferentiated transformed human promonocytic (THP)-1 cell model system. Expression of the functional MIE proteins was achieved with a replication-defective adenovirus vector, Ad-IE1/2, which contains the MIE gene locus. Expression of the MIE proteins by Ad-IE1/2 prior to HCMV infection induced viral early gene expression accompanied by an increase in active chromatin signals. Expression of the anti-apoptotic protein encoded by UL37x1 increased viral early gene expression. However, viral DNA replication and production of infectious virus was not detected. As expected, cellular differentiation with phorbol 12-myristate 13-acetate and hydrocortisone induced virus production. Cellular differentiation is required for efficient viral reactivation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenoviridae / genetics
  • Cell Differentiation
  • Cell Line
  • Chromatin / genetics
  • Chromatin / metabolism
  • Cytomegalovirus / genetics*
  • Cytomegalovirus / growth & development
  • Cytomegalovirus / physiology
  • DNA, Viral / genetics
  • DNA, Viral / metabolism
  • Gene Expression Regulation, Viral*
  • Genetic Vectors / genetics
  • Humans
  • Immediate-Early Proteins / genetics
  • Immediate-Early Proteins / metabolism*
  • RNA, Viral / genetics
  • RNA, Viral / metabolism
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • Viral Proteins / genetics
  • Viral Proteins / metabolism*

Substances

  • Chromatin
  • DNA, Viral
  • IE1 protein, cytomegalovirus
  • IE2 protein, Cytomegalovirus
  • Immediate-Early Proteins
  • RNA, Viral
  • Trans-Activators
  • UL37 protein, Human herpesvirus 5
  • Viral Proteins