| Type de publication : |
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Articles dans des revues avec comité de lecture |
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| Domaine : |
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Sciences du Vivant/Biochimie, Biologie Moléculaire
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| Titre : |
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Structural effects of amino acid variations between B and CRF02-AG HIV-1 integrases. |
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| Auteur(s) : |
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Isabelle Malet ( ) 1, 2, Cathia Soulie 2, Luba Tchertanov 3, 4, Anne Derache 1, 2, Bahia Amellal 2, Ousmane Traore 5, Anne Simon 6, Christine Katlama 1, Jean-François Mouscadet 3, Vincent Calvez 1, 2, Anne-Geneviève Marcelin 1, 2 |
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| Laboratoire : |
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| 1 : |
Hôpital Pitié-Salpétrière |
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Assistance publique - Hôpitaux de Paris (AP-HP) – Université Pierre et Marie Curie (UPMC) - Paris VI |
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47-83, boulevard de l'Hôpital 75651 Paris Cedex 13 |
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France |
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| 2 : |
Service de Virologie |
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Assistance publique - Hôpitaux de Paris (AP-HP) |
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AP-HP, Hôpital Pitié-Salpêtrière, Service de Virologie, Paris, France |
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France |
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| 3 : |
Laboratoire de Biotechnologie et Pharmacologie génétique Appliquée (LBPA) |
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http://www.lbpa.ens-cachan.fr/ |
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CNRS : UMR8113 – École normale supérieure de Cachan - ENS Cachan |
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61 AVENUE DU PRESIDENT WILSON 94235 CACHAN CEDEX |
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France |
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| 4 : |
Laboratoire de Chimie Bioorganique et Analytique |
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Faculté des Sciences et Techniques de Mohamedia |
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Faculté des Sciences et Techniques, BP 146, Mohamedia, Morocco. |
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Maroc |
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| 5 : |
Centre de soins |
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Bamako |
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Centre d'Ecoute, de Soins, d'Animations et de Conseils, Bamako, Mali |
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Mali |
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| 6 : |
Service de médecine interne [Pitié-Salpétrière] |
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Assistance publique - Hôpitaux de Paris (AP-HP) – Hôpital Pitié-Salpêtrière – Université Pierre et Marie Curie (UPMC) - Paris VI |
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47-83, boulevard de l'Hôpital 75651 PARIS Cedex 13 |
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France |
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| Résumé : |
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HIV-1 integrase is one of the three essential enzyme required for viral replication and has a great potential as a novel target for anti-HIV drugs. The sequence variability of the entire integrase (IN) was examined in HIV-1 subtype B and CRF02-AG antiretroviral na? infected patients for the presence of naturally occurring polymorphisms IN gene sequences and protein structures from both subtypes were compared. The phylogenetic analysis showed a total concordance between the 3 pol gene sequences for patients identified as subtype B whereas 3% of patients identified as CRF02-AG showed a mixture of subtypes. The analysis of IN aa sequences showed that 13 positions (K/R14, V/I31, L/I101, T/V112, T/A124, T/A125, G/N134, I/V135, K/T136, V/I201, T/S206, L/I234, and S/G283) differed between subtypes B and CRF02-AG. As observed in the 3D model of the preintegration complex, these differences may impact the functional property of IN. The fact that most variations were grouped suggests that some of them are linked together through compensatory mechanisms. This comparison allowed us to identify several variations of amino acids in HIV-1 IN subtype CRF02-AG that could have a putative impact on anti-integrase sensitivity. In particular, the region formed by Thr125, Thr124, Val31 contains at least one residue, T125, which variation has been involved in eliciting resistance to the naphtyridine carboxamide L870,810 IN inhibitor. In conclusion, virological response to anti-integrase should be studied carefully, according to the subtype, in clinical trials. |
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Langue du texte
intégral : |
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Anglais |
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| Journal : |
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| Journal of Medical Virology (J Med Virol) |
| Publisher |
Wiley-Blackwell |
| ISSN |
0146-6615 (eISSN : 1096-9071) |
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| Audience : |
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internationale |
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| Date de publication : |
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05/2008 |
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| Volume : |
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80 |
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| Numéro : |
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5 |
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| Page, identifiant, ... : |
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754-61 |
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| Descripteur(s) MeSH : |
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Amino Acid Sequence – Amino Acid Substitution – Drug Resistance – Viral – HIV Infections – HIV Integrase – HIV-1 – Humans – Models – Molecular – Molecular Sequence Data – Phylogeny – Polymorphism – Genetic – Protein Structure – Tertiary – RNA – Sequence Alignment – Sequence Analysis – DNA – United States |
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