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Aquarius helicase facilitates HIV-1 integration into R-loop enriched genomic regions.

Carlotta Penzo1, Ilayda Özel1,2, Moreno Martinovic3,4

  • 1Department of Infectious Diseases, Center for Integrative Infectious Disease Research (CIID), Integrative Virology, Heidelberg University, Heidelberg, Germany.

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|August 20, 2025
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Summary
This summary is machine-generated.

Genomic RNA:DNA hybrids (R-loops) are key targets for HIV-1 integrase (IN) in active genes. Resolving these R-loops, with help from Aquarius (AQR), is crucial for efficient viral integration and may offer new therapeutic strategies.

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Area of Science:

  • Molecular Biology
  • Virology
  • Genetics

Background:

  • HIV-1 integration into host DNA is essential for viral replication, mediated by viral integrase (IN).
  • IN typically targets intronic regions of transcriptionally active genes, but the precise mechanisms remain unclear.
  • Understanding these integration preferences is critical for addressing HIV-1 latency and developing therapies.

Purpose of the Study:

  • To investigate the role of genomic RNA:DNA hybrids (R-loops) in HIV-1 integration.
  • To identify host factors that facilitate HIV-1 integration at specific genomic sites.
  • To explore the therapeutic potential of targeting the integration process.

Main Methods:

  • Utilized ex vivo activated human primary CD4+ T cells to study HIV-1 integration.
  • Mapped R-loops and HIV-1 integration sites using genomic techniques.
  • Investigated the interaction between HIV-1 integrase (IN) and Aquarius (AQR).
  • Assessed the impact of AQR knockout on viral integration efficiency and site selection.

Main Results:

  • Genomic R-loops were found to preferentially map to intronic regions of active genes, typical HIV-1 integration sites.
  • HIV-1 integrase (IN) binds to R-loops, and their resolution enhances viral integration in vitro.
  • Aquarius (AQR), an RNA helicase, associates with IN and its activity promotes integration into R-loop substrates.
  • AQR knockout in CD4+ T cells impaired integration efficiency and shifted integration sites away from R-loops.

Conclusions:

  • R-loops are preferential targets for HIV-1 integration, mediated by IN.
  • The RNA helicase Aquarius (AQR) plays a significant role in facilitating HIV-1 integration at R-loops.
  • These findings highlight potential therapeutic targets for controlling HIV-1 latency and reactivation.