Human Cytomegalovirus miR-US25-1 Targets the GTPase RhoA To Inhibit CD34(+) Hematopoietic Progenitor Cell Proliferation To Maintain the Latent Viral Genome

Human cytomegalovirus (HCMV) microRNAs play essential roles in latency and reactivation in CD34(+) hematopoietic progenitor cells (HPCs) via regulation of viral and cellular gene expression. In the present study, we show that HCMV miR-US25-1 targets RhoA, a small GTPase required for CD34(+) HPC self-renewal, proliferation, and hematopoiesis. Expression of miR-US25-1 impairs signaling through the nonmuscle myosin II light chain, which leads to a block in cytokinesis and an inhibition of proliferation. Moreover, infection with an HCMV mutant lacking miR-US25-1 resulted in increased proliferation of CD34(+) HPCs and a decrease in the proportion of genome-containing cells at the end of latency culture. These observations provide a mechanism by which HCMV limits proliferation to maintain latent viral genomes in CD34(+) HPCs.