A myeloid progenitor cell line capable of supporting human cytomegalovirus latency and reactivation, resulting in infectious progeny

J Virol. 2012 Sep;86(18):9854-65. doi: 10.1128/JVI.01278-12. Epub 2012 Jul 3.


Human cytomegalovirus (HCMV) is a herpesvirus that establishes a lifelong, latent infection within a host. At times when the immune system is compromised, the virus undergoes a lytic reactivation producing infectious progeny. The identification and understanding of the biological mechanisms underlying HCMV latency and reactivation are not completely defined. To this end, we have developed a tractable in vitro model system to investigate these phases of viral infection using a clonal population of myeloid progenitor cells (Kasumi-3 cells). Infection of these cells results in maintenance of the viral genome with restricted viral RNA expression that is reversed with the addition of the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA, also known as PMA). Additionally, a latent viral transcript (LUNA) is expressed at times where viral lytic transcription is suppressed. Infected Kasumi-3 cells initiate production of infectious virus following TPA treatment, which requires cell-to-cell contact for efficient transfer of virus to other cell types. Importantly, lytically infected fibroblast, endothelial, or epithelial cells can transfer virus to Kasumi-3 cells, which fail to initiate lytic replication until stimulated with TPA. Finally, inflammatory cytokines, in addition to the pharmacological agent TPA, are sufficient for transcription of immediate-early (IE) genes following latent infection. Taken together, our findings argue that the Kasumi-3 cell line is a tractable in vitro model system with which to study HCMV latency and reactivation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Cell Line
  • Cytokines / physiology
  • Cytomegalovirus / genetics
  • Cytomegalovirus / pathogenicity*
  • Cytomegalovirus / physiology*
  • Cytomegalovirus Infections / virology
  • DNA, Viral / genetics
  • Gene Expression / drug effects
  • Genes, Immediate-Early
  • Genome, Viral
  • Humans
  • Inflammation Mediators / physiology
  • Models, Biological
  • Myeloid Progenitor Cells / drug effects
  • Myeloid Progenitor Cells / physiology
  • Myeloid Progenitor Cells / virology*
  • Tetradecanoylphorbol Acetate / pharmacology
  • Virus Activation / genetics
  • Virus Activation / physiology
  • Virus Latency / genetics
  • Virus Latency / physiology
  • Virus Replication / genetics
  • Virus Replication / physiology


  • Cytokines
  • DNA, Viral
  • Inflammation Mediators
  • Tetradecanoylphorbol Acetate