Abstract
Cytomegalovirus (CMV) gene expression is repressed in latency due to heterochromatinization of viral genomes. In murine CMV (MCMV) latently infected mice, viral genomes are bound to histones with heterochromatic modifications, to enzymes that mediate these modifications, and to adaptor proteins that may recruit co-repressor complexes. Kinetic analyses of repressor binding show that these repressors are recruited at the earliest time of infection, suggesting that latency may be the default state. Kidney transplantation leads to epigenetic reprogramming of latent viral chromatin and reactivation of immediate early gene expression. Inflammatory signaling pathways, which activate transcription factors that regulate the major immediate early promoter (MIEP), likely mediate the switch in viral chromatin.
Highlights
Human cytomegalovirus (HCMV) is an important opportunistic pathogen of the beta family of herpesviruses
The initial binding and subsequent loss of repressors in infected mice is consistent with host-mediated repression of murine cytomegalovirus (MCMV) gene expression through heterochromatinization of incoming viral genomes and subsequent de-repression by viral proteins, as seen in cell culture models of HCMV
Our preliminary studies indicate that the NF- B and AP-1 sites are not occupied in kidneys of MCMV latently infected mice, but the NF- B p65 subunit and the AP-1 junD subunit are recruited to the major immediate early promoter (MIEP) when latently infected kidneys are transplanted into allogeneic recipients
Summary
Human cytomegalovirus (HCMV) is an important opportunistic pathogen of the beta family of herpesviruses. CMV has the ability to establish lifelong latent infection, in which viral DNA is present, but replicating virus is not detectable, and to reactivate from latency. The similarities between HCMV and MCMV of relevance here include (i) ability to establish latency and to reactivate [9,10,11]; (ii) hierarchical control of viral gene expression, in which the immediate early (ie) genes activate expression of the early genes, leading to viral DNA replication, late gene expression, and viral assembly; (iii) structure, function, and organization of immediate early genes [9,11,12], and regulation of the major immediate early promoter, which controls major ie gene expression [13,14]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
