TY  - JOUR
AU  - Penzo, Carlotta
AU  - Özel, Ilayda
AU  - Martinovic, Moreno
AU  - Kuzman, Maja
AU  - Glavas, Dunja
AU  - Stanic, Mia
AU  - Reichenbach, Thomas
AU  - Müller, Thorsten G
AU  - Rheinberger, Mona
AU  - Godarzi, Negar
AU  - Lapaillerie, Delphine
AU  - Srezovic, Bruno
AU  - dell'Oca, Maria Chiara
AU  - Lange, Laura C
AU  - Sadhu, Lopamudra
AU  - de Castro, Ines J
AU  - Shytaj, Iart Luca
AU  - Forcato, Mattia
AU  - Laketa, Vibor
AU  - Bicciato, Silvio
AU  - Vlahovicek, Kristian
AU  - Fackler, Oliver T
AU  - Lucic, Bojana
AU  - Pena, Vlad
AU  - Kräusslich, Hans-Georg
AU  - Parissi, Vincent
AU  - Lusic, Marina
TI  - Aquarius helicase facilitates HIV-1 integration into R-loop enriched genomic regions.
JO  - Nature microbiology
VL  - 10
IS  - 9
SN  - 2058-5276
CY  - London
PB  - Nature Publishing Group
M1  - DKFZ-2025-01732
SP  - 2306-2322
PY  - 2025
N1  - 2025 Sep;10(9):2306-2322
AB  - HIV-1 integration into host chromosomes, essential for viral replication, is catalysed by viral integrase (IN). IN recurrently targets intronic regions of transcriptionally active genes, but a detailed understanding of this process is still unclear. Here, using ex vivo activated human primary CD4+T cells, we find that genomic RNA:DNA hybrids (R-loops) preferentially map to intronic regions of active genes that are typical HIV-1 integration sites. IN binds R-loops and their resolution enhances viral integration in vitro. We identify Aquarius (AQR), the splicing RNA helicase of the pentameric intron binding complex (IBC), which associates with IN and show that its RNA:DNA helicase activity promotes integration into hybrid substrates in vitro. Knockout of AQR in primary CD4+ T cells impaired overall integration efficiency, while sequencing of remaining integrations mapped them to intergenic and R-loop distal regions. These findings may have important implications for HIV-1 latency and reactivation and may thus identify novel therapeutic targets.
LB  - PUB:(DE-HGF)16
C6  - pmid:40836041
DO  - DOI:10.1038/s41564-025-02089-2
UR  - https://inrepo02.dkfz.de/record/303963
ER  -