Human cytomegalovirus latency, reactivation and disease
Human cytomegalovirus (HCMV) is an opportunistic human pathogen that establishes a lifelong latent infection that can periodically reactivate which, if unchecked by a robust immune response, can result in severe disease in immuno-compromised patients. Following primary infection of healthy individuals, human cytomegalovirus (HCMV) is met with a robust immune response resulting in an asymptomatic infection and subsequent establishment of latency. To date, HCMV remains one of the leading viral agents of disease in immuno-suppressed transplant patients and is a cause of severe morbidity in late stage AIDS sufferers and cancer patients.
The threat from HCMV is exacerbated by the dual threat of primary infection/re-infection, and virus reactivation within the host. Since many instances of virus disease result from HCMV reactivation, many studies have analysed the regulation of latency and reactivation using experimental models. An informed consensus supports the myeloid lineage as an important site of HCMV latency and carriage and that terminal myeloid differentiation is needed for HCMV reactivation. A recurrent theme in HCMV latency/reactivation, this differentiation-dependent permissiveness also applies to lytic infection. Latently infected cells are, by definition, unable to support the viral lytic transcription program – pivotal to this is failure of IE gene expression.
Reactivation of latent virus in myeloid progenitor cells is concomitant with cellular differentiation through regulation of the MIEP by chromatin remodelling. This study analyses the expression of the latent gene transcript UL81-82as (LUNA). LUNA is expressed in latently infected CD34+ cells and expression decreases as CD34+ cells differentiate to immature dendritic cells. Upon maturation (and HCMV reactivation) a second wave of transcription occurs consistent with expression during lytic infection also. Furthermore, it shows that the LUNA promoter is associated with acetylated histones during HCMV latency in experimentally and naturally infected CD34+ cells thus suggesting that latent gene promoters are, like the MIEP, regulated by post-translational modifications of their associated histone proteins.
Related:
- Human Cytomegalovirus-encoded microRNA regulates expression of multiple genes involved in replication
- Human cytomegalovirus and the cell cycle
Tags: Biology, Herpes, HIV/AIDS, latency, Medicine, Microbiology, Science, Virology, virus
