title: Human cytomegalovirus: Latency and reactivation in the myeloid lineage.
abstract: Human cytomegalovirus (HCMV) persists as a sub-clinical, lifelong infection in the human host which is maintained at least in part by its carriage in the absence of detectable infectious virus: a hallmark of latent infection. In contrast, reactivation from latency in immuno-compromised individuals can result in serious disease. Understanding virus latency and reactivation, therefore, is essential for a full understanding of the biology and pathogenesis of this persistent human herpesvirus. However, the precise cellular sites in which HCMV is carried and the mechanisms regulating its latency and reactivation, during natural infection, remain poorly understood. Recent work, however, has led to a consensus opinion that cells of the myeloid lineage are one site of carriage of HCMV in vivo and that in myeloid dendritic cell (DC) progenitors the viral genome is carried latently in the absence of virus lytic gene expression. In contrast, differentiation of these cells to a mature DC phenotype is linked with reactivation of infectious virus resulting from differentiation-dependent chromatin remodelling of the viral major immediate-early promoter. Thus there is a crucial link between the differentiation of myeloid cells and transcriptional reactivation of latent virus which is likely to play a key role in viral pathogenesis.
authors.affiliation: Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2QQ, UK. js@mole.bio.cam.ac.uk
authors.forename: John
authors.initials: J
authors.lastname: Sinclair
mesh_terms: D002454:Cell Differentiation; D003587:Cytomegalovirus / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity* / Q000502:physiology*; D003586:Cytomegalovirus Infections / Q000821:virology; D003713:Dendritic Cells / Q000166:cytology / Q000821:virology; D015967:Gene Expression Regulation, Viral; D006801:Humans; D022423:Myeloid Cells / Q000166:cytology / Q000821:virology*; D014775:Virus Activation; D017735:Virus Latency