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000303963 1001_ $$aPenzo, Carlotta$$b0
000303963 245__ $$aAquarius helicase facilitates HIV-1 integration into R-loop enriched genomic regions.
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000303963 520__ $$aHIV-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.
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000303963 7001_ $$0P:(DE-He78)f344ca1e8e6547684a24a41ac89faedb$$aÖzel, Ilayda$$b1$$udkfz
000303963 7001_ $$aMartinovic, Moreno$$b2
000303963 7001_ $$00000-0002-7490-450X$$aKuzman, Maja$$b3
000303963 7001_ $$aGlavas, Dunja$$b4
000303963 7001_ $$00000-0003-2149-2916$$aStanic, Mia$$b5
000303963 7001_ $$aReichenbach, Thomas$$b6
000303963 7001_ $$00000-0002-4197-6224$$aMüller, Thorsten G$$b7
000303963 7001_ $$aRheinberger, Mona$$b8
000303963 7001_ $$aGodarzi, Negar$$b9
000303963 7001_ $$aLapaillerie, Delphine$$b10
000303963 7001_ $$aSrezovic, Bruno$$b11
000303963 7001_ $$00009-0003-3722-7057$$adell'Oca, Maria Chiara$$b12
000303963 7001_ $$aLange, Laura C$$b13
000303963 7001_ $$aSadhu, Lopamudra$$b14
000303963 7001_ $$00000-0001-8710-3667$$ade Castro, Ines J$$b15
000303963 7001_ $$00000-0002-9980-1275$$aShytaj, Iart Luca$$b16
000303963 7001_ $$aForcato, Mattia$$b17
000303963 7001_ $$aLaketa, Vibor$$b18
000303963 7001_ $$00000-0002-1944-7078$$aBicciato, Silvio$$b19
000303963 7001_ $$aVlahovicek, Kristian$$b20
000303963 7001_ $$00000-0003-2982-4209$$aFackler, Oliver T$$b21
000303963 7001_ $$aLucic, Bojana$$b22
000303963 7001_ $$aPena, Vlad$$b23
000303963 7001_ $$aKräusslich, Hans-Georg$$b24
000303963 7001_ $$00000-0003-1661-7841$$aParissi, Vincent$$b25
000303963 7001_ $$00000-0002-0120-3569$$aLusic, Marina$$b26
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