Our work "Aquarius helicase facilitates HIV-1 integration into R-loop enriched genomic regions" is out @natmicrobiol.nature.com, showing HIV-1 integration into R-loop genomic regions upon their resolution by cellular splicing helicase Aquarius (AQR) of the Intron Binding Complex (IBC)🧵.

Our study, conducted in primary human CD4+ T cells, shows that HIV-1 preferentially integrates into intronic regions of transcriptionally active genes, where RNA:DNA hybrids (R-loops) are often created.

We demonstrate that HIV-1 integrase binds directly to R-loops, suggesting that the RNA component of chromatin acts as a guiding signal — effectively a molecular “bait” — for integration.

RNA helicase Aquarius (AQR), a component of the Intron Binding Complex (IBC), is an essential host factor for R-loop integration, as it unwinds R-loops and interacts with integrase to facilitate precise targeting of the viral genome.

AQR knock out in primary T cells hampers integration efficiency and shifts remaining integration to intergenic and R-loop–depleted regions, demonstrating that R-loop-rich sites are preferred by HIV-1 and are facilitated by host RNA metabolism.

Our discovery offers a critical new angle for HIV intervention. By interfering with the host mechanisms that support targeted integration, we hope to affect viral persistence without the need for lifelong daily treatment.