Levels of human cytomegalovirus miR-US25-1-5p and miR-UL112-3p in serum extracellular vesicles from infants with HCMV active infection are significantly correlated with liver damage.

Abstract

Human cytomegalovirus (HCMV)-encoded microRNAs (miRNAs) are involved in posttranscriptional regulation of gene expression. Extracellular vesicles (EVs) can incorporate miRNAs. Relationship between HCMV infection and miRNAs in EVs remains unknown. EVs were isolated from supernatants of human embryonic lung fibroblasts (HELF) cells. Profiles of miRNAs in EVs were analyzed by deep sequencing. Dynamics of candidate viral miRNAs transportation via EVs was investigated using TaqMan PCR. Levels of candidate viral miRNAs in serum EVs from infants with HCMV active infection were detected and analyzed with their clinical index levels. A total of 16 HCMV miRNAs were found in EVs from infected HELF. Levels of miR-US25-1-5p and miR-UL112-3p in EVs increased at 6h post-infection and were correlated with those in cells (for miR-US25-1-5p: r2 = 0.9375, p value < 0.05; for miR-UL112-3p: r2 = 0.7557, p value < 0.05). Viral miRNAs were transported into recipient cells at 2h post-incubation. Moreover, levels of miR-US25-1-5p in serum EVs showed positive correlations with serum levels of γ-glutamyl transpeptidase, direct bilirubin, and total bile acid. Levels of miR-UL112-3p in serum EVs showed a positive correlation with serum levels of direct bilirubin. HCMV miRNAs could be transported to uninfected cells via EVs. Levels of miR-US25-1-5p and miR-UL112-3p in serum EVs from infants with HCMV active infection were significantly correlated with liver damage.