pia N, Clotet B, Martinez MA; International Conference on AIDS.
Int Conf AIDS. 2002 Jul 7-12; 14: abstract no. TuPeA4395.
Fundacio irsiCaixa, Badalona, Spain
BACKGROUND: Assays for drug resistance testing in human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2) infection and treatment should be incorporated into patient management. In HIV-2 infected patients, data on drug resistance is very limited and no resistance mutation partners have been described. We present here a bacteriophage lambda-based genetic screening system as an in vitro method for the characterization of the activity and phenotype of HIV-2 protease. METHODS: This genetic screening system is based on the bacteriophage lambda cI-cro regulatory circuit in which the viral repressor cI is specifically cleaved to initiate the lysogenic to lytic switch. The introduction of an HIV-1 protease in a wild-type phage will cleave a mutant cI repressor, which contains a specific HIV-1 protease cleavage site, allowing the phage to go into the lytic replication cycle. Lambda phages that encode HIV-1 proteases are inhibited in a dose-dependent manner by different HIV-1 protease inhibitors. This method has been now adapted to HIV-2 protease. RESULTS: Using the above system, IC50 values for ritonavir, indinavir, nelfinavir and saquinavir were calculated. HIV-1 and HIV-2 showed similar sensitivity to indinavir (IC50HIV-1, 2.36 microM and IC50HIV-2, 2.07 microM), nelfinavir (IC50HIV-1, 1.8 microM and IC50HIV-2, 1.56 microM) and ritonavir (IC50HIV-1, 6.5 microM and IC50HIV-2, 6.6 microM). In contrast, HIV-2 showed a nine-fold increase in the sensitivity to saquinavir (IC50HIV-1, 3.1 microM and IC50HIV-2, 0.35 microM). CONCLUSIONS: We describe here a rapid method to study the susceptibility of HIV-2 protease to different protease inhibitors, which can be used for the clinical management of HIV-2 infected patients.
Publication Types:
Keywords:
- Bacteriophage lambda
- Genetic Screening
- Genetic Techniques
- HIV Protease
- HIV Protease Inhibitors
- HIV-1
- HIV-2
- Humans
- In Vitro
- Indinavir
- Inhibitory Concentration 50
- Laboratory Techniques and Procedures
- Motor Activity
- Nelfinavir
- Phenotype
- Protease Inhibitors
- Ritonavir
- Saquinavir
- genetics
Other ID:
UI: 102252392
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