The HB-19 pseudopeptide 5[Kpsi(CH2N)PR]-TASP inhibits attachment of T lymophocyte- and macrophage-tropic HIV to permissive cells.
The HB-19 pseudopeptide 5[Kpsi(CH2N)PR]-TASP[psi(CH2N) indicating a reduced peptide bond], which binds the cell surface-expressed nucleolin, is a potent inhibitor of HIV infection. Here, by using primary T lymphocyte cultures and an experimental cell model to monitor HIV entry, we show that HB-19 inhibits in a dose-dependent manner both T lymphocyte- and macrophage-tropic HIV isolates. Similar positively charged control pseudopeptides have no effect 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 VSV envelope glycoproteins, confirm the specific nature of this inhibitor against the entry process mediated by the HIV envelope glycoproteins. Finally, association of low doses of HB-19 with beta-chemokines or AZT results in an increased inhibitory effect on HIV infection. HB-19 has no inhibitory effect 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, even after washing cells to remove away the unbound pseudopeptide. Under such conditions, the attachment of HIV particles to cells is inhibited as efficiently as by neutralizing monoclonal antibodies directed against the V3 loop. In view of its specific mode of action on various HIV isolates, HB-19 represents a potential anti-HIV drug.
Nisole
S
S
Unité de Virologie et Immunologie Cellulaire, URA CNRS 1930, Institut Pasteur, Paris, France.
Krust
B
B
Dam
E
E
Bianco
A
A
Seddiki
N
N
Loaec
S
S
Callebaut
C
C
Guichard
G
G
Muller
S
S
Briand
J P
JP
Hovanessian
A G
AG
D019380:Anti-HIV Agents / Q000737:chemistry / Q000494:pharmacology*; D002462:Cell Membrane / Q000821:virology; D002478:Cells, Cultured; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000494:pharmacology; D004352:Drug Resistance, Microbial; D015497:HIV-1 / Q000187:drug effects* / Q000302:isolation & purification / Q000502:physiology; D015498:HIV-2 / Q000187:drug effects* / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000821:virology; D019402:Macrophage Inflammatory Proteins / Q000494:pharmacology; D008264:Macrophages / Q000821:virology; D015394:Molecular Structure; D010455:Peptides; D011506:Proteins / Q000737:chemistry / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000821:virology*; D014771:Virion / Q000187:drug effects / Q000378:metabolism; D015215:Zidovudine / Q000494:pharmacology
D019380:Anti-HIV Agents; D054407:Chemokine CCL4; D018946:Chemokine CCL5; C121944:HB-19 peptide; D019402:Macrophage Inflammatory Proteins; D010455:Peptides; D011506:Proteins; D015215:Zidovudine