Résumé
The V3 loop-mimicking pseudopeptide 5[K psi(CH2N)PR]-TASP [psi(CH2N) representing a reduced peptide bond], which presents pentavalently the tripeptide K psi(CH2N)PR, is a potent inhibitor of HIV entry. By its capacity to bind specifically protein components on the cell surface, 5[K psi (CH2N)PR]-TASP blocks the attachment of virus particles to permissive CD4+ cells. Here, the inhibitory effect of 5[K psi(CH2N)PR]-TASP was investigated in monocyte-derived macrophages (MDMs) infected by the monocytotropic HIV-1Ba-L isolate. We show that 5[K psi(CH2N)PR]-TASP inhibits HIV-1Ba-L infection in a dose-dependent manner, with more than 90% inhibition at 2 mu M concentration. On the other hand, the control 5[QPQ]-TASP construct and the monovalent K psi(CH2N)PR tripeptide have no effect even at high concentrations. Under such experimental conditions, the biotin-labeled 5[K psi(CH2N)PR]-TASP, but not the K psi (CH2N)PR construct, binds specifically to the surface of MDMs and forms a stable complex with the cell surface-expressed nucleolin, as has been demonstrated to be the case in peripheral blood mononuclear cells. Infection of MDMs by HIV-1Ba-L could also be inhibited by beta-chemokines RANTES and MIP-1beta. Interestingly, association of low concentrations of 5[K psi(CH2N)PR]-TASP and beta-chemokines results in a synergistic inhibitory effect on HIV infection compared with the effect observed with each reagent alone. The inhibitory effect of 5[K psi(CH2N)PR]-TASP in primary macrophage cultures point out its potential as an anti-HIV drug in cells, which are the natural viral targets.