hsa-miR-181-5p inhibits human immunodeficiency virus type 1 replication by downregulating DDX3X expression

HIV-1 infection affects expression profiles of microRNA. miR-181 is found negatively correlated with HIV-1 viral load. This study aimed to explain that miR-181 targets DDX3X, a host factor involved in HIV-1 nuclear export, thereby inhibiting HIV-1 replication.

To verify our hypothesis, first, the relationship between miR-181 expression, DDX3X expression, and HIV-1 viral load was analyzed. Second, miR-181 mimics were transfected into Jurkat cells infected with wild pNL4-3 strain or H9-IIIB cells with HIV-1 replication-competent for HIV-1 viral protein P24(Gag) detection. Besides the reporter gene plasmid containing the DDX3X mRNA sequence was transfected into 293T cells to demonstrate the targeting of miR-181 to the DDX3X mRNA. Finally, the spliced, unspliced, or incompletely spliced HIV-1 transcripts and HIV-1 Tat, Rev, and Gag mRNA were also detected after miR-181 transfection.

Our result proved that miR-181 significantly reduced the HIV-1 viral protein Gag(P24) level and targeted DDX3X mRNA 3'-UTR, inhibiting the unspliced or incompletely spliced HIV-1 mRNA's nuclear export.

Our results confirmed that miR-181 is involved in HIV-1 viral replication in lymphocytes by downregulating DDX3X expression. The research provides a research basis for future HIV-1 antiviral research.