La N-glycosylation du VIH : du modèle expérimental à l'application thérapeutique.
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Human. immunodeficiency virus type-1 (HIV) envelope precursor glycoprotein (gp160) is cleaved into gp120 and gp41 ; gp120 and gp41 are responsible for HIV tropism for CD4+ cells and for viral and cell membrane fusion leading to virus entry into cells, respectively. The functional role of gp160 N-linked glycans (CHO), which represent 50 % of its MW, was studied. During the biosynthesis, it was shown that CHO clusters of gp160 induce the bioactive folding of both gp41 and gp120 : the interaction between abnormally glycosylated gp120 and its CD4 receptor was altered and the accessibility of the V3 loop, a region that plays a key role in membrane fusion was diminished. Such modified properties could account for the impairment of HIV-1 infectivity by glycosylation inhibitors, the prototypes of potential anti-HIV drugs. Similarly, mutation of the gp41 cluster of glycosylation sites inhibited gP160 cleavage and abolished gp41-mediated membrane fusion. In contrast, after biosynthesis, CHO present on mature viral gp120 and gp41 are involved neither in their bioactivity nor in their conformation : the ability of deglycosylated virus to bind and to infect CD4+ cells was reduced by only 10 fold. CHO are then necessary to create but not to maintain the functional conformation Of HIV env products.