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  2. Pinpointing recurrent proviral integration sites in new models for latent HIV-1 infection

Pinpointing recurrent proviral integration sites in new models for latent HIV-1 infection

  • Virus Res. 2018 Apr 2;249:69-75. doi: 10.1016/j.virusres.2018.03.007.
Ulrike C Lange 1 Julia K Bialek 2 Thomas Walther 3 Joachim Hauber 4
Affiliations

Affiliations

  • 1 Heinrich Pette Institute - Leibniz Institute for Experimental Virology, 20251 Hamburg, Germany; Department of Anesthesiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Center for Infection Research (DZIF), Partner Site Hamburg, Germany. Electronic address: [email protected].
  • 2 Heinrich Pette Institute - Leibniz Institute for Experimental Virology, 20251 Hamburg, Germany; Department of Anesthesiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
  • 3 Heinrich Pette Institute - Leibniz Institute for Experimental Virology, 20251 Hamburg, Germany.
  • 4 Heinrich Pette Institute - Leibniz Institute for Experimental Virology, 20251 Hamburg, Germany; Center for Infection Research (DZIF), Partner Site Hamburg, Germany.
Abstract

HIV Infection is characterized by accumulation of proviral sequences within the human host genome. Integration of viral-derived DNA occurs at preferential loci, suggesting a site-specific crosstalk between viral sequences and human genes. We here describe a genome engineering workflow to generate models for HIV-1 Infection that for the first time recapitulate proviral integration at selected genomic loci and provide unique tools to study effects of HIV proviral integration site choice. Using this workflow, we have derived two BACH2-HIV-1 reporter models that mimic largely latent integration in the clinically relevant BACH2 gene locus, which has been associated with recurrent integration and HIV-reservoir maintenance in chronically infected patients.

Keywords

CRISPR/Cas9; Genome engineering; HIV integration; HIV latency; HIV model systems.

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