Comparative biochemical analysis of HIV-1 subtype B and C integrase enzymes

被引:40
作者
Bar-Magen, Tamara [1 ]
Sloan, Richard D. [1 ]
Faltenbacher, Verena H. [1 ]
Donahue, Daniel A. [1 ,2 ]
Kuhl, Bjoern D. [1 ,3 ]
Oliveira, Maureen [1 ]
Xu, Hongtao [1 ]
Wainberg, Mark A. [1 ,2 ,3 ]
机构
[1] McGill Univ, AIDS Ctr, Lady Davis Inst, Jewish Gen Hosp, Montreal, PQ, Canada
[2] McGill Univ, Dept Microbiol & Immunol, Montreal, PQ H3A 2T5, Canada
[3] McGill Univ, Div Expt Med, Montreal, PQ H3A 2T5, Canada
基金
加拿大健康研究院;
关键词
DNA INTEGRATION; STRAND-TRANSFER; IN-VITRO; VIRUS; RESISTANCE; RALTEGRAVIR; PROTEIN; INHIBITORS; MUTATIONS; ELVITEGRAVIR;
D O I
10.1186/1742-4690-6-103
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Background: Integrase inhibitors are currently being incorporated into highly active antiretroviral therapy (HAART). Due to high HIV variability, integrase inhibitor efficacy must be evaluated against a range of integrase enzymes from different subtypes. Methods: This study compares the enzymatic activities of HIV-1 integrase from subtypes B and C as well as susceptibility to various integrase inhibitors in vitro. The catalytic activities of both enzymes were analyzed in regard to each of 3' processing and strand transfer activities both in the presence and absence of the integrase inhibitors raltegravir (RAL), elvitegravir (EVG), and MK-2048. Results: Our results show that integrase function is similar with enzymes of either subtype and that the various integrase strand transfer inhibitors (INSTIs) that were employed possessed similar inhibitory activity against both enzymes. Conclusion: This suggests that the use of integrase inhibitors against HIV-1 subtype C will result in comparable outcomes to those obtained against subtype B infections.
引用
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页数:10
相关论文
共 32 条
[1]   Disulfide-linked integrase oligomers involving C280 residues are formed in vitro and in vivo but are not essential for human immunodeficiency virus replication [J].
Bischerour, J ;
Leh, H ;
Deprez, E ;
Brochon, JC ;
Mouscadet, JF .
JOURNAL OF VIROLOGY, 2003, 77 (01) :135-141
[2]   HIV-1 subtype C viruses rapidly develop K65R resistance to tenofovir in cell culture [J].
Brenner, Bluma G. ;
Oliveira, Maureen ;
Doualla-Bell, Florence ;
Moisi, Daniela D. ;
Ntemgwa, Michel ;
Frankel, Fernando ;
Essex, Max ;
Wainberg, Mark A. .
AIDS, 2006, 20 (09) :F9-F13
[3]   RETROVIRAL DNA INTEGRATION DIRECTED BY HIV INTEGRATION PROTEIN INVITRO [J].
BUSHMAN, FD ;
FUJIWARA, T ;
CRAIGIE, R .
SCIENCE, 1990, 249 (4976) :1555-1558
[4]   DOMAINS OF THE INTEGRASE PROTEIN OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 RESPONSIBLE FOR POLYNUCLEOTIDYL TRANSFER AND ZINC-BINDING [J].
BUSHMAN, FD ;
ENGELMAN, A ;
PALMER, I ;
WINGFIELD, P ;
CRAIGIE, R .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (08) :3428-3432
[6]   REVERSAL OF INTEGRATION AND DNA SPLICING MEDIATED BY INTEGRASE OF HUMAN-IMMUNODEFICIENCY-VIRUS [J].
CHOW, SA ;
VINCENT, KA ;
ELLISON, V ;
BROWN, PO .
SCIENCE, 1992, 255 (5045) :723-726
[7]   Subgroup and resistance analyses of raltegravir for resistant HIV-1 infection [J].
Cooper, David A. ;
Steigbigel, Roy T. ;
Gatell, Jose M. ;
Rockstroh, Jurgen K. ;
Katlama, Christine ;
Yeni, Patrick ;
Lazzarin, Adriano ;
Clotet, Bonaventura ;
Kumar, Princy N. ;
Eron, Joseph E. ;
Schechter, Mauro ;
Markowitz, Martin ;
Loutfy, Mona R. ;
Lennox, Jeffrey L. ;
Zhao, Jing ;
Chen, Joshua ;
Ryan, Desmond M. ;
Rhodes, Rand R. ;
Killar, John A. ;
Gilde, Lucinda R. ;
Strohmaier, Kim M. ;
Meibohm, Anne R. ;
Miller, Michael D. ;
Hazuda, Daria J. ;
Nessly, Michael L. ;
DiNubile, Mark J. ;
Isaacs, Robin D. ;
Teppler, Hedy ;
Nguyen, Bach-Yen .
NEW ENGLAND JOURNAL OF MEDICINE, 2008, 359 (04) :355-365
[8]   Prediction of the Virological Response to Etravirine in Clinical Practice: Comparison of Three Genotype Algorithms [J].
Cotte, Laurent ;
Trabaud, Mary-Anne ;
Tardy, Jean-Claude ;
Brochier, Corinne ;
Gilibert, Rene-Pierre ;
Miailhes, Patrick ;
Trepo, Christian ;
Andre, Patrice .
JOURNAL OF MEDICAL VIROLOGY, 2009, 81 (04) :672-677
[9]  
Debyser Z, 2000, METH MOL B, V160, P139
[10]   Integrase and integration: biochemical activities of HIV-1 integrase [J].
Delelis, Olivier ;
Carayon, Kevin ;
Saib, Ali ;
Deprez, Eric ;
Mouscadet, Jean-Francois .
RETROVIROLOGY, 2008, 5 (1)