miR-223 inhibits dengue virus replication by negatively regulating the microtubule-destabilizing protein STMN1 in EAhy926 cells

Abstract

The pathogenesis of dengue virus (DENV) infection is not completely understood. Endothelial cells may act as a target of the virus and be involved in disease pathogenesis. Therefore, the identification of host cell components involved in DENV replication would provide useful information for better understanding DENV infection. In this study, a significantly decreased level of miR-223 was found in DENV2-infected EAhy926 cells, a human endothelial-like cell line, whereas miR-223 overexpression inhibited DENV2 replication. Furthermore, we identified that miR-223 directly targeted the 3' untranslated region (3'UTR) of the messenger RNA (mRNA) for microtubule-destabilizing protein stathmin 1 (STMN1), thereby reducing its mRNA and protein levels. The depletion of miR-223 or overexpression of STMN1 enhanced DENV2 replication, whereas the opposite (increased miR-223 or decreased STMN1) suppressed DENV2 replication, indicating that miR-223 down-regulates STMN1 expression by targeting the 3'UTR of the STMN1 gene to inhibit DENV2 replication. Finally, we demonstrated that two transcription factors, C/EBPα and E2F1, are involved in the regulation of miR-223 levels after DENV2 infection in EAhy926 cells. Collectively, our results suggest that miR-223 may act as a novel antiviral factor, which may open an avenue to limit DENV infection.

Keywords: C/EBPα; Dengue virus; E2F1; STMN1; miR-223.