Disruption of LEDGF/p75-directed integration derepresses antisense transcription of the HIV-1 genome.

Autor:	Tedbury PR; Center for ViroScience and Cure, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine; Atlanta, GA, USA.; Children's Healthcare of Atlanta; Atlanta, GA, USA., Mahboubi D; Center for ViroScience and Cure, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine; Atlanta, GA, USA.; Children's Healthcare of Atlanta; Atlanta, GA, USA., Puray-Chavez M; Department of Molecular Microbiology & Immunology, University of Missouri School of Medicine; Columbia, MO, USA.; C.S. Bond Life Sciences Center, University of Missouri; Columbia, MO, USA., Shah R; Center for ViroScience and Cure, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine; Atlanta, GA, USA.; Children's Healthcare of Atlanta; Atlanta, GA, USA., Ukah OB; Department of Molecular Microbiology & Immunology, University of Missouri School of Medicine; Columbia, MO, USA.; C.S. Bond Life Sciences Center, University of Missouri; Columbia, MO, USA., Wahoski CC; Center for ViroScience and Cure, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine; Atlanta, GA, USA.; Children's Healthcare of Atlanta; Atlanta, GA, USA., Fadel HJ; Division of Infectious Diseases, Anschutz Medical Campus, University of Colorado School of Medicine; Aurora, CO, USA., Poeschla EM; Division of Infectious Diseases, Anschutz Medical Campus, University of Colorado School of Medicine; Aurora, CO, USA., Gao X; Center for ViroScience and Cure, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine; Atlanta, GA, USA.; Children's Healthcare of Atlanta; Atlanta, GA, USA., McFadden WM; Center for ViroScience and Cure, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine; Atlanta, GA, USA.; Children's Healthcare of Atlanta; Atlanta, GA, USA., Gaitanidou M; Center for ViroScience and Cure, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine; Atlanta, GA, USA.; Children's Healthcare of Atlanta; Atlanta, GA, USA., Kesesidis N; Center for ViroScience and Cure, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine; Atlanta, GA, USA.; Children's Healthcare of Atlanta; Atlanta, GA, USA., Kirby KA; Center for ViroScience and Cure, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine; Atlanta, GA, USA.; Children's Healthcare of Atlanta; Atlanta, GA, USA., Vanderford TH; Division of Microbiology and Immunology, Emory National Primate Research Center, Emory Vaccine Center, Emory University; Atlanta, GA, USA., Kvaratskhelia M; Division of Infectious Diseases, Anschutz Medical Campus, University of Colorado School of Medicine; Aurora, CO, USA., Achuthan V; Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute; Boston, MA, USA., Behrens RT; Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison; Madison, WI, USA., Engelman AN; Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute; Boston, MA, USA., Sarafianos SG; Center for ViroScience and Cure, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine; Atlanta, GA, USA.; Children's Healthcare of Atlanta; Atlanta, GA, USA.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2024 Dec 06. Date of Electronic Publication: 2024 Dec 06.
DOI:	10.1101/2024.12.06.627169
Abstrakt:	Disruption of HIV-1 Integrase (IN) interactions with the host-factor Lens Epithelium-Derived Growth Factor (LEDGF)/p75 leads to decreased, random integration, increased latent infection, and described here, accumulation of HIV-1 antisense RNA (asRNA). asRNA increase was observed following interruptions of IN-LEDGF/p75 interactions either through pharmacologic perturbations of IN-LEDGF/p75 by treatment with allosteric HIV-1 integrase inhibitors (ALLINIs) or in cell lines with LEDGF genetic knockout. Additionally, by impairing Tat-dependent HIV transcription, asRNA abundance markedly increases. Illumina sequencing characterization of asRNA transcripts in primary T cells infected in the presence of ALLINIs showed that most initiate from within the HIV-1. Overall, loss of IN-LEDGF/p75 interactions increase asRNA abundance. Understanding the relationship between ALLINIs, integration sites, asRNA, and latency could aid in future therapeutic strategies. Competing Interests: Competing interests: Authors declare that they have no competing interests.
Databáze:	MEDLINE
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