This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Colson, P.
Right arrow Articles by Tamalet, C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Colson, P.
Right arrow Articles by Tamalet, C.

 Previous Article  |  Next Article 

Journal of Clinical Microbiology, February 2004, p. 570-577, Vol. 42, No. 2
0095-1137/04/$08.00+0     DOI: 10.1128/JCM.42.2.570-577.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Polymorphism and Drug-Selected Mutations in the Protease Gene of Human Immunodeficiency Virus Type 2 from Patients Living in Southern France

P. Colson,1 M. Henry,1 C. Tourres,1 D. Lozachmeur,1 H. Gallais,2 J. A. Gastaut,3 J. Moreau,4 and C. Tamalet1*

Laboratoire de Bactériologie-Virologie, Centre Hospitalo-Universitaire Timone et CNRS UMR 6020 IFR48, Université de la Méditerranée,1 Service de Maladies Infectieuses, Hôpital Conception,2 Service d'Hématologie, Hôpital Sainte-Marguerite,3 Service de Maladies Infectieuses, Hôpital Nord, Marseilles, France4

Received 1 April 2003/ Returned for modification 11 August 2003/ Accepted 27 September 2003

The susceptibility of human immunodeficiency virus type 2 (HIV-2) to protease inhibitors (PI) is largely unknown. We studied HIV-2 protease genes from 21 HIV-2-infected patients who were exposed or not exposed to PI. The aim of this study was (i) to characterize the polymorphism of HIV-2 protease in the absence of drug, (ii) to know whether the HIV-2 protease gene naturally harbors HIV-1 drug resistance codons, and (iii) to identify mutations emerging under PI-selective pressure. Sixty-five HIV-2 RNA or proviral DNA samples were directly sequenced from the plasma or peripheral blood mononuclear cells of 8 patients who had received PI and 13 patients who had never received any antiretroviral. In untreated patients, the highest amino acid variability in HIV-2 protease was observed at positions 14, 40, 43, 46, 65 and 70, and seven codons (10V, 32I, 36I, 46I, 47V, 71V, and 73A) associated with drug resistance in HIV-1 were highly prevalent. In addition, at six positions (positions 7, 46, 62, 71, 90, and 99), the amino acid variability or the amino acid frequencies or both differed significantly in PI-treated and untreated patients, suggesting that mutations 7K->R, 46V->I, 62V->A/T, 71V->I, 90L->M and 99L->F were occurring under PI-selective pressure. At these positions, at least one sample simultaneously harbored both wild-type and mutated codons, while substitutions at positions 62, 71, 90, and 99 were confirmed in a longitudinal analysis. Moreover, the presence of codons 46I and 99F in the absence of drug in HIV-2 subtype B proteases may reflect natural resistance to PI. In conclusion, the present study revealed that HIV-2 strains harbor specific patterns of natural polymorphism and resistance.

* Corresponding author. Mailing address: Laboratoire de Bactériologie-Virologie, Centre Hospitalo-Universitaire Timone, 264 rue Saint-Pierre 13385 Marseille Cedex 05, France. Phone: 33 (0)4 91 38 55 22. Fax: 33 (0)4 91 77 92 66. E-mail: ctamalet{at}ap-hm.fr.

Journal of Clinical Microbiology, February 2004, p. 570-577, Vol. 42, No. 2
0095-1137/04/$08.00+0     DOI: 10.1128/JCM.42.2.570-577.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Ntemgwa, M. L., Toni, T. d., Brenner, B. G., Camacho, R. J., Wainberg, M. A. (2009). Antiretroviral Drug Resistance in Human Immunodeficiency Virus Type 2. Antimicrob. Agents Chemother. 53: 3611-3619 [Full Text]  
  • Jallow, S., Alabi, A., Sarge-Njie, R., Peterson, K., Whittle, H., Corrah, T., Jaye, A., Cotten, M., Vanham, G., McConkey, S. J., Rowland-Jones, S., Janssens, W. (2009). Virological Response to Highly Active Antiretroviral Therapy in Patients Infected with Human Immunodeficiency Virus Type 2 (HIV-2) and in Patients Dually Infected with HIV-1 and HIV-2 in The Gambia and Emergence of Drug-Resistant Variants. J. Clin. Microbiol. 47: 2200-2208 [Abstract] [Full Text]  
  • Jallow, S., Kaye, S., Schutten, M., Brandin, E., Albert, J., McConkey, S. J., Corrah, T., Whittle, H., Vanham, G., Rowland-Jones, S., Janssens, W. (2007). Development and Evaluation of an Oligonucleotide Ligation Assay for Detection of Drug Resistance-Associated Mutations in the Human Immunodeficiency Virus Type 2 pol Gene. J. Clin. Microbiol. 45: 1565-1571 [Abstract] [Full Text]  
  • Ntemgwa, M., Brenner, B. G., Oliveira, M., Moisi, D., Wainberg, M. A. (2007). Natural Polymorphisms in the Human Immunodeficiency Virus Type 2 Protease Can Accelerate Time to Development of Resistance to Protease Inhibitors. Antimicrob. Agents Chemother. 51: 604-610 [Abstract] [Full Text]  
  • Rodes, B., Sheldon, J., Toro, C., Jimenez, V., Alvarez, M. A., Soriano, V. (2006). Susceptibility to protease inhibitors in HIV-2 primary isolates from patients failing antiretroviral therapy. J Antimicrob Chemother 57: 709-713 [Abstract] [Full Text]  
  • Gatanaga, H., Das, D., Suzuki, Y., Yeh, D. D., Hussain, K. A., Ghosh, A. K., Mitsuya, H. (2006). Altered HIV-1 Gag Protein Interactions with Cyclophilin A (CypA) on the Acquisition of H219Q and H219P Substitutions in the CypA Binding Loop. J. Biol. Chem. 281: 1241-1250 [Abstract] [Full Text]  
  • Damond, F., Brun-Vezinet, F., Matheron, S., Peytavin, G., Campa, P., Pueyo, S., Mammano, F., Lastere, S., Farfara, I., Simon, F., Chene, G., Descamps, D. (2005). Polymorphism of the Human Immunodeficiency Virus Type 2 (HIV-2) Protease Gene and Selection of Drug Resistance Mutations in HIV-2-Infected Patients Treated with Protease Inhibitors. J. Clin. Microbiol. 43: 484-487 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»