Human Cytomegalovirus Replication Enhanced By Placental MicroRNAs

ABSTRACT Placental trophoblasts constitute the interface between the fetal and maternal environments and physically prevent maternal–fetal viral transmission. However, congenital human cytomegalovirus (HCMV) infection in the early stages of pregnancy results in severe symptoms in the fetus. HCMV is the most common causative agent of intrauterine infection. To clarify the etiology of congenital HCMV infection, we focused on how the placental environment affects HCMV infection. We investigated the role of microRNAs (miRNAs), which are highly and specifically expressed in placental trophoblasts. The transfection of trophoblast‐specific C19MC miRNAs, encoded by the chromosome 19 miRNA cluster, markedly enhanced HCMV Immediate Early (IE) gene expression and subsequent viral production. However, the expression of the herpes simplex virus type‐1 IE gene was not changed by C19MC‐BAC transfection. From among 46427 mapped genes, we identified that the expression of RAC2, a Rac family small GTPase, was markedly suppressed with an independent genetic hierarchical cluster by C19MC‐BAC transfection. The suppression of RAC2 expression enhanced HCMV IE gene expression. Here, we propose the hypothesis that the placental environment contributes to HCMV‐specific replication via the trophoblast‐specific miRNA‐mediated downregulation of RAC2 expression.