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@ARTICLE{Penzo:303963,
author = {C. Penzo and I. Özel$^*$ and M. Martinovic and M. Kuzman
and D. Glavas and M. Stanic and T. Reichenbach and T. G.
Müller and M. Rheinberger and N. Godarzi and D. Lapaillerie
and B. Srezovic and M. C. dell'Oca and L. C. Lange and L.
Sadhu and I. J. de Castro and I. L. Shytaj and M. Forcato
and V. Laketa and S. Bicciato and K. Vlahovicek and O. T.
Fackler and B. Lucic and V. Pena and H.-G. Kräusslich and
V. Parissi and M. Lusic},
title = {{A}quarius helicase facilitates {HIV}-1 integration into
{R}-loop enriched genomic regions.},
journal = {Nature microbiology},
volume = {10},
number = {9},
issn = {2058-5276},
address = {London},
publisher = {Nature Publishing Group},
reportid = {DKFZ-2025-01732},
pages = {2306-2322},
year = {2025},
note = {2025 Sep;10(9):2306-2322},
abstract = {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.},
cin = {B087},
ddc = {570},
cid = {I:(DE-He78)B087-20160331},
pnm = {312 - Funktionelle und strukturelle Genomforschung
(POF4-312)},
pid = {G:(DE-HGF)POF4-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:40836041},
doi = {10.1038/s41564-025-02089-2},
url = {https://inrepo02.dkfz.de/record/303963},
}