Virally induced changes in cellular microRNAs maintain latency of human cytomegalovirus in CD34⁺ progenitors

Abstract

One site of latency of human cytomegalovirus (HCMV; human herpesvirus 5) is known to be CD34(+) haematopoietic progenitor cells, and it is likely that carriage of latent virus has profound effects on cellular gene expression in order to optimize latency and reactivation. As microRNAs (miRNAs) play important roles in regulating stem-cell gene expression, this study asked whether latent carriage of HCMV led to changes in cellular miRNA expression. A comprehensive miRNA screen showed the differential regulation of a number of cellular miRNAs during HCMV latency in CD34(+) progenitor cells. One of these, hsa-miR-92a, was robustly decreased in three independent miRNA screens. Latency-induced change in hsa-miR-92a results in an increase in expression of GATA-2 and subsequent increased expression of cellular IL-10, which aids the maintenance of latent viral genomes in CD34(+) cells, probably resulting from their increased survival.