Apabetalone mediates HIV-1 transcriptional activation and clearance of latently infected cells via LncRNA OSER1-AS1.

PURPOSE: To explore the effect of Apabetalone on activating HIV-1 virus transcription and its molecular mechanism.

METHODS

Peripheral blood mononuclear cells(PBMCs) latently infected with HIV-1 and J-Lat 10.6 cells were divided into two groups: a blank control group and an Apabetalone-treated group. After 48 h of culture with Apabetalone, bioinformatics and qRT-PCR were performed. Recombinant lentiviral vectors containing OSER1-AS1 and CDK9, along with empty vectors, were transfected into the cells for subsequent green fluorescent protein(GFP) fluorescence detection, cell cycle analysis, and apoptosis assays.

RESULTS

Apabetalone efficiently activated HIV-1 viral transcription in J-Lat 10.6 and PBMC cells, increased the G0/G1 ratio of cells, and induced apoptosis. Apabetalone also downregulated the expression levels of MYC and p-Rb, and upregulated the expression levels of Tat and P21. Silencing OSER1-AS1 reduced apabetalone activation of HIV-1 transcription and inhibited apoptosis.

CONCLUSION

Apabetalone enhances HIV-1 transcription by upregulating OSER1-AS1 expression, thereby promoting Tat-CDK9 binding.