Analysis of latent viral gene expression in natural and experimental latency models of human cytomegalovirus and its correlation with histone modifications at a latent promoter

Abstract

Human cytomegalovirus (HCMV) is an opportunistic human pathogen that establishes a lifelong latent infection, which can reactivate periodically. If unchecked by a robust immune response, this reactivation can result in severe disease in immunocompromised patients. Reactivation of latent virus in myeloid progenitor cells is concomitant with cellular differentiation through regulation of the major immediate-early promoter (MIEP) by chromatin remodelling. In this study, we analysed the expression of the latent gene transcript UL81-82as (LUNA). LUNA is expressed in latently infected CD34(+) cells and its 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. Furthermore, we show 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.