Journal
JOURNAL OF GENERAL VIROLOGY
Volume 86, Issue -, Pages 2949-2954Publisher
MICROBIOLOGY SOC
DOI: 10.1099/vir.0.81161-0
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Funding
- MRC [G9202171, G9800943] Funding Source: UKRI
- Medical Research Council [G9202171, G9800943] Funding Source: researchfish
- Medical Research Council [G9202171, G9800943] Funding Source: Medline
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Human cytomegalovirus (HCMV) is a frequent cause of major disease following primary infection or reactivation from latency in immunocompromised patients. Infection of non-permissive mononuclear cells is used for analyses of HCMV latency in vitro. Using this approach, it is shown here that repression of lytic gene expression following experimental infection of CD34(+) cells, a site of HCMV latency in vivo, correlates with recruitment of repressive chromatin around the major immediate-early promoter (MIEP). Furthermore, long-term culture of CD34+ cells results in carriage of viral genomes in which the MIEP remains associated with transcriptionally repressive chromatin. Finally, specific differentiation of long-term cultures of infected CD34+ cells to mature dendritic cells results in acetylation of histones bound to the MIEP, concomitant loss of heterochromatin protein 1 and the reactivation of HCMV. These data are consistent with ex vivo analyses of latency and may provide a model for further analyses of the mechanisms involved during latency and reactivation.
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