It is now well appreciated that microRNAs (miRNAs) play a critical role in the lifecycles of many herpes viruses. The human cytomegalovirus (HCMV) replication cycle varies significantly depending on the cell type infected, with lytic replication occurring in fully-differentiated cells such as fibroblasts, endothelial cells, or macrophages, and latent infection occurring in less-differentiated CD14+ monocytes and CD34+ hematopoietic progenitor cells where viral gene expression is severely diminished and progeny virus is not produced. Given their non-immunogenic nature and their capacity to target numerous cellular and viral transcripts, miRNAs represent a particularly advantageous means for HCMV to manipulate viral gene expression and cellular signaling pathways during lytic and latent infection. This review will focus on our current knowledge of HCMV miRNA viral and cellular targets, and discuss their importance in lytic and latent infection, highlight the challenges of studying HCMV miRNAs, and describe how viral miRNAs can help us to better understand the cellular processes involved in HCMV latency.
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