Sites de clivage de gag et résistance du VIH aux inhibiteurs de la protéase

The role of the human immunodeficiency virus type 1 protease is to cleave Gag and Gag-Pol polyproteinic precursors at specific sites called cleavage sites to release the structural proteins (p7, p17 and p24) and enzymes (protease, reverse transcriptase and integrase) of the virus. Ribosomal −1 frameshifting mediated by a downstream signal is required for translating the messenger RNA in these precursors. At time of virological failure, mutations associated with resistance to PI in protease gene are selected. These substitutions are responsible for a decrease in viral replicative capacity. Mutations at group specific antigen (gag) cleavage sites can be selected in virus from patients failing PI containing regimen. Studies have shown that presence of gag cleavage sites substitutions in the absence of mutations in the protease gene might be associated with virological failure.