HIV-2 Protease resistance defined in yeast cells

Area of Science:

• Virology
• Biochemistry
• Drug Resistance

Background:

• HIV-2 Protease inhibitors show cross-resistance with HIV-1 drugs.
• Therapeutic failure in HIV-2 is linked to drug-resistant viral strains.
• Understanding specific mutations is crucial for effective HIV-2 treatment.

Purpose of the Study:

• To establish a yeast-based experimental model for studying HIV-2 Protease.
• To determine mutations conferring resistance to Protease Inhibitors in HIV-2.
• To assess the susceptibility of HIV-2 Protease variants to specific drugs.

Main Methods:

• Expression of HIV-2 Protease in a yeast system.
• Assessing yeast cell viability as a measure of Protease activity.
• Determining IC50 values for anti-retroviral drugs against HIV-2 Protease.
• Comparing drug susceptibility of clinical HIV-2 Protease isolates to a wild-type strain.

Main Results:

• HIV-2 Protease activity in yeast leads to cell death, inhibitable by anti-retroviral drugs.
• Dose-dependent inhibition allowed for IC50 value determination.
• The L90M substitution in a primary HIV-2 isolate altered susceptibility to Saquinavir but not Lopinavir.

Conclusions:

• A functional yeast assay can identify drug resistance mutations in HIV-2 Protease.
• The L90M substitution is a key mutation affecting Saquinavir efficacy in HIV-2.
• This yeast expression system provides a strategy for defining amino acid substitutions conferring HIV-2 Protease resistance.