A major concern in the antiretroviral (ARV) treatment of HIV infections with protease inhibitors (PI) is the emergence of resistance, which results from the selection of distinct mutations within the viral protease (PR) gene. Among patients who do not respond to treatment with the PI nelfinavir (NFV), the D30N mutation is often observed. However, several reports have shown that D30N emerges wit...

To study variability in reverse transcriptase (RT) and protease (PR) genes of HIV-1 isolated from recently infected patients identified between 1997 and 2003, sequences were obtained on the RT and PR genes of viruses harvested from plasma of 121 non-treated subjects who had undergone primary HIV infection. The degree of dissimilarity between the viruses studied and a reference HIV-1 subtype B s...

HIV-1 pol gene sequencing is now used routinely in France to identify mutations associated with resistance to reverse transcriptase (RT) or protease (PR) inhibitors. These sequences may also provide other information, such as the HIV-1 subtype. HIV-1 subtyping was compared using the RT and PR gene sequences to heteroduplex mobility assay (HMA) of the envelope gene. The RT and PR genes of 51 sam...

The aspartyl proteinase (PR) encoded by the feline immunodeficiency virus (FIV) was prepared by total chemical synthesis. The 116-amino-acid polypeptide chain was assembled in a stepwise fashion using a Boc chemistry solid-phase peptide synthesis approach and subsequently folded into the biologically active dimeric proteinase. The synthetic enzyme showed proteolytic activity against a variety o...

Introduction of a number of HIV-1 protease (PR) inhibitors as anti-AIDS drugs has drastically changed the clinical prognosis for the outcome of this disease, from almost invariably lethal to chronic. This achievement also represented the first major success of structure-based drug design, encouraging the use of similar approaches to other major diseases, such as cancer. We have now identified a...

The proteolytic processing of human immunodeficiency virus (HIV) particles mediated by the viral pol-encoded protease (PR) is essential for viral infectivity. The pol coding sequence partially overlaps with the gag coding sequence and is translated as a Gag-Pol polyprotein precursor. Within Gag-Pol, the C-terminal p6(gag) domain is replaced by a transframe peptide referred to as p6*, which sepa...

Ordered and accurate processing of the human immunodeficiency virus type 1 (HIV-1) GagPol polyprotein precursor by a virally encoded protease is an indispensable step in the appropriate assembly of infectious viral particles. The HIV-1 protease (PR) is a 99-amino-acid enzyme that is translated as part of the GagPol precursor. Previously, we have demonstrated that the initial events in precursor...

The HIV-1 nucleocapsid is formed during protease (PR)-directed viral maturation, and is transformed into pre-integration complexes following reverse transcription in the cytoplasm of the infected cell. Here, we report a detailed transmission electron microscopy analysis of the impact of HIV-1 PR and reverse transcriptase (RT) on nucleocapsid plasticity, using in vitro reconstitutions. After bin...

One of the biggest challenges in the "in silico" screening of enzyme ligands is to have a protocol that could predict the ligand binding free energies. In our group we have developed a very simple screening function (referred to as solvent accessibility free energy of binding predictor, SAFE_p) which we have applied previously to the study of peptidic HIV-1 protease (HIV-1 PR) inhibitors and la...

HIV-1 protease (PR) mediates the proteolytic processing of virus particles during or after virus budding. PR activation is thought to be triggered by appropriate Gag-Pol/Gag-Pol interaction; factors affecting this interaction either enhance or reduce PR-mediated cleavage efficiency, resulting in markedly reduced virion production or the release of inadequately processed virions. We previously s...