Evolution of 2-long terminal repeat (2-LTR) episomal HIV-1 DNA in raltegravir-treated patients and in in vitro infected cells
| Autor: | Guerric Anies, Bernard Masquelier, Linda Wittkop, Rodolphe Thiébaut, Sandrine Reigadas, Marie-Line Andreola, Patricia Recordon-Pinson, Ophélie Cosnefroy, Hervé Fleury |
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| Přispěvatelé: | Microbiologie cellulaire et moléculaire et pathogénicité (MCMP), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Epidémiologie et Biostatistique [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Santé Publique, d'Epidémiologie et de Développement (ISPED), Université Bordeaux Segalen - Bordeaux 2, Variabilité génomique des virus, Université Bordeaux Segalen - Bordeaux 2-IFR66, Service de virologie et d'immunologie biologique, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Coordination Régionale de la lutte contre l'infection due au VIH (COREVIH), COREVIH |
| Rok vydání: | 2010 |
| Předmět: |
MESH: Sequence Analysis
DNA viruses Integrase inhibitor HIV Infections MESH: HIV-1 chemistry.chemical_compound Pharmacology (medical) MESH: Anti-HIV Agents MESH: Evolution Molecular Recombination Genetic 0303 health sciences MESH: HIV Long Terminal Repeat biology MESH: HIV Infections Viral Load Long terminal repeat Pyrrolidinones 3. Good health Integrase Infectious Diseases [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology Lentivirus MESH: DNA Circular MESH: Recombination Genetic DNA Circular MESH: Viral Load medicine.drug Plasmids Microbiology (medical) Anti-HIV Agents In Vitro Techniques MESH: Pyrrolidinones Virus Evolution Molecular 03 medical and health sciences MESH: Plasmids Raltegravir Potassium medicine Humans 030304 developmental biology HIV Long Terminal Repeat Pharmacology MESH: Humans 030306 microbiology Sequence Analysis DNA biology.organism_classification Raltegravir Virology MESH: DNA Viral MESH: Hela Cells chemistry DNA Viral biology.protein HIV-1 DNA Ex vivo HeLa Cells |
| Zdroj: | Journal of Antimicrobial Chemotherapy Journal of Antimicrobial Chemotherapy, Oxford University Press (OUP), 2010, 65 (3), pp.434-7. ⟨10.1093/jac/dkp473⟩ Journal of Antimicrobial Chemotherapy; Vol 65 |
| ISSN: | 1460-2091 0305-7453 |
| DOI: | 10.1093/jac/dkp473⟩ |
| Popis: | International audience; OBJECTIVES: Our aim was to analyse the evolution of HIV-1 2-long terminal repeat (2-LTR) circular DNA in vitro and ex vivo in the presence of raltegravir. PATIENTS AND METHODS: Twenty-five patients starting a raltegravir-based regimen were included. Total HIV-1 DNA and 2-LTR DNA were quantified at baseline and in follow-up samples up to month 12. The effect of raltegravir on the formation of 2-LTR circles was evaluated in HeLa P4 cells. The effect of raltegravir was also investigated by sequence analysis of the 2-LTR circle junctions. RESULTS: Among 21 patients with undetectable 2-LTR DNA at baseline, 7 had detectable 2-LTR DNA during the follow-up. Three of four patients with detectable 2-LTR DNA at baseline had undetectable 2-LTR DNA during the follow-up (P = 0.27). The mean 2-LTR level increased significantly (+0.07 log(10)/month, P = 0.02) in raltegravir-treated patients, and a 2-LTR increase was also observed in raltegravir-treated HeLa P4 cells, with a peak at 3 days post-infection. 2-LTR DNA showed a high prevalence of deletions ex vivo (64.5%) and in vitro (50%) in the presence of raltegravir, which was not statistically different from the prevalence in untreated patients or cells. CONCLUSIONS: In antiretroviral-experienced patients receiving raltegravir, 2-LTR DNA increased while total HIV-1 DNA decreased over time. The frequent rearrangements found in 2-LTR sequences warrant further investigations to determine the dynamics of evolution of unintegrated HIV-1 DNA. |
| Databáze: | OpenAIRE |
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