Human Cytomegalovirus Genome Replication and Maintenance During Latent Infection
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Human cytomegalovirus (HCMV) is a ubiquitous herpesvirus that causes severe disease and death in immune-compromised people. HCMV, like all herpesviruses, establishes a lifelong latent infection associated with the lack of production of infectious virus and the maintenance of the HCMV viral genome in CD34 (+) hematopoietic progenitor cells, and CD14 (+) monocytes. Although many aspects of the mechanism involved in HCMV latency remain unknown, recently published results from our laboratory show the entire HCMV latent transcriptome in experimental as well as naturally infected CD34 (+) and CD14 (+) cells. The elucidation of all of the viral encoded factors during HCMV latent infection is a major step, however there is a critical need to identify HCMV genomic DNA elements that contribute to viral genome persistence. More recent work from our laboratory has now identified the terminal repeat (TR) element of HCMV as an origin of latent viral DNA replication. Furthermore, we have identified viral and cellular factors necessary for maintaining HCMV latency. Together, these results define, for the first time, vital elements in a model of HCMV latent infection.