Investigating Transposable Elements and Mobile DNA as Targets of Integration for Establishing HIV Reservoirs in the Brain (R61/R33 - Clinical Trial Optional)

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oMany substances of abuse, including cocaine, methamphetamine, and several opioids exert powerful environmental insults on genomic DNA in the brain that induce expression of transposable elements and other mobile DNA. Transposable elements and mobile DNA, which comprise almost 50% of the human genome, are typically silenced through strong epigenetic modifications. When transposable elements and mobile DNA become active in people who use drugs of abuse, they potentially provide multiple integration sites for HIV in microglia. HIV integration into these unstable regions could lead to major chromosomal rearrangements and global dysregulation of transcription, ultimately contributing to HIV-associated Neurocognitive Disorder (HAND) and providing a mechanism by which drugs of abuse increase the probability of reactivating microglial HIV reservoirs. Understanding the factors that influence HIV integration in these microglial reservoirs is crucial to developing next-generation HIV therapies and potential cures. This concept addresses these gaps by fostering studies aimed at providing a deeper understanding of the complex interplay among HIV, substances of abuse, inflammation, and disease progression.

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