The HB-19 pseudopeptide S[K psi(CH2N)PR]-TASP inhibits attachment of T lymphocyte- and macrophage-tropic HIV to permissive cells

The HE-19 pseudopeptide S[K psi(CH2N)PR]-TASP [psi(CH2N) indicating a reduc ed peptide bond], which binds the cell surface-expressed nucleolin, is a po tent inhibitor of HIV infection. Here, by using primary T lymphocyte cultur es and an experimental cell model to monitor HIV entry, we show that HE-19 inhibits in a dose-dependent manner both T lymphocyte- and macrophage-tropi c HIV isolates. Similar positively charged control pseudopeptides have no e ffect on HIV infection even at high concentrations. These observations, and the fact that HB-19 has no effect on SIV-mac and HIV-1 pseudotyped with VS V envelope glycoproteins, confirm the specific nature of this inhibitor aga inst the entry process mediated by the HIV envelope glycoproteins, Finally, association of low doses of HE-19 with beta-chemokines or AZT results in a n increased inhibitory effect on HIV infection. HE-19 has no inhibitory eff ect when added to cells a few hours after HIV entry. On the other hand, in HB-19-pretreated cells, the inhibitory effect persists for several hours, e ven after washing cells to remove away the unbound pseudopeptide. Under suc h conditions, the attachment of HN particles to cells is inhibited as effic iently as by neutralizing monoclonal antibodies directed against the V3 loo p. In view of its specific mode of action on various HIV isolates, HE-19 re presents a potential anti-HIV drug.