New Insights into How HIV Integrates into Human DNA via R-Loop Mechanism

Researchers at the German Center for Infection Research (DZIF) and Heidelberg University Hospital have uncovered a novel mechanism by which HIV-1 integrates into the human genome. The study, led by Dr. Marina Lusic, reveals that the virus exploits specific molecular structures called RNA:DNA hybrids, or R-loops, which are prevalent in active, non-coding regions of the genome. These structures act as signposts for HIV-1's integrase enzyme, guiding the virus to insertion sites. The key cellular partner in this process is the enzyme Aquarius (AQR), which assists HIV in recognizing and unwinding R-loops, facilitating viral integration.

The team demonstrated that HIV does not randomly insert into the genome but uses these R-loops to target specific regions. When AQR activity is inhibited, the rate of viral integration significantly decreases, and the remaining integrations occur in regions with fewer R-loops. This discovery highlights a vulnerability in the HIV life cycle and opens avenues for targeted therapies that could disrupt this integration process.

Understanding this mechanism is crucial in the ongoing fight against HIV, especially considering the challenges posed by viral reservoirs that evade current treatments. Conventional antiretroviral therapy effectively suppresses viral replication but requires lifelong adherence, and interruptions can lead to viral rebound and resistant strains. By targeting the specific molecular structures HIV exploits for integration, scientists hope to develop strategies to limit or eliminate these reservoirs.

Overall, this research provides valuable insights into the detailed interactions between HIV-1 and host cellular machinery. It suggests potential new targets for therapies aimed at preventing the virus from establishing persistent reservoirs, moving closer to functional cures or eradication strategies.

Source: https://medicalxpress.com/news/2025-09-hiv-genome-decodes-previously-unknown.html