title: A myeloid progenitor cell line capable of supporting human cytomegalovirus latency and reactivation, resulting in infectious progeny.
abstract: 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.
authors: Department of Molecular Genetics, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.
authors: Christine M
authors: CM
authors: O'Connor
authors: Eain A
authors: EA
authors: Murphy
mesh_terms: D001483:Base Sequence; D002460:Cell Line; D016207:Cytokines / Q000502:physiology; D003587:Cytomegalovirus / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology*; D003586:Cytomegalovirus Infections / Q000821:virology; D004279:DNA, Viral / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D017781:Genes, Immediate-Early; D016679:Genome, Viral; D006801:Humans; D018836:Inflammation Mediators / Q000502:physiology; D008954:Models, Biological; D023461:Myeloid Progenitor Cells / Q000187:drug effects / Q000502:physiology / Q000821:virology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014775:Virus Activation / Q000235:genetics / Q000502:physiology; D017735:Virus Latency / Q000235:genetics / Q000502:physiology; D014779:Virus Replication / Q000235:genetics / Q000502:physiology
chemical_list: D016207:Cytokines; D004279:DNA, Viral; D018836:Inflammation Mediators; D013755:Tetradecanoylphorbol Acetate