HIV-1 Tat and cocaine coexposure impacts piRNAs to affect astrocyte energy metabolism.

To understand the effect of HIV infection and cocaine exposure on piRNA expression in human primary astrocytes. We used small RNA sequencing analysis to investigate the impacts of HIV-1 Tat and cocaine coexposure on the expression of piRNAs in human primary astrocytes. We identified 27,700 piRNAs and analyzed them by small RNA next-generation sequencing. A total of 239 piRNAs were significantly altered by HIV-1 Tat and cocaine coexposure. We also identified PIWIL1, PIWIL2, PIWIL3 and PIWIL4 as interacting partners of piRNAs that were affected by cocaine and HIV-1 Tat coexposure. Epigenetic changes in the expression levels of these piRNA targets were associated with Kyoto Encyclopedia of Genes and Genomes pathways of energy metabolism and neurodegeneration. These findings provide evidence that cocaine exposure and HIV infection affect the expression levels of piRNA, PIWIL1, PIWIL2, PIWIL3 and PIWIL4.