AEGiS-12IAC: The binding of HIV to permissive cells is coordinated by interactions of gp120 with both CD4 and V3 loop binding proteins.

12th International AIDS Conference

Geneva, Switzerland - June 28-July 3, 1998

The binding of HIV to permissive cells is coordinated by interactions of gp120 with both CD4 and V3 loop binding proteins.

Int Conf AIDS 1998 Jun 28-Jul 3; 12:5 (abstract no. 11114)

Callebaut C, Blanco J, Krust B, Seddiki N, Muller S, Briand JP, Hovanessian AG
Institut Pasteur, Unite V.I.C., Paris, France.

OBJECTIVES: To demonstrate the distinct role of the V3 loop of gp120 in the binding of HIV particles to permissive CD4 positive cells.

BACKGROUND: Neutralizing mAbs against the V3 loop, block the binding of HIV virions to permissive cells without affecting the potential capacity of gp120 to interact with CD4 (J. Virol. 71, 8289, 1997). Interestingly, the anti-HIV pseudopeptide 5[K iota PR]-TASP which mimics the V3 loop (Virology 218, 181, 1996), binds cell-surface protein(s) other than CD4 and chemokine receptors, and inhibits the binding of HIV virions to CD4+ target cells (J. Biol. Chem. 272, 7159, 1997).

RESULTS: The pseudopeptide TASP inhibits viral entry in different types of cells infected by T lymphocyte- and macrophage-tropic HIV-1 and HIV-2 isolates. TASP has no effect on SIV mac and HIV-1 pseudotypes expressing either Mo-MLV or VSV-G envelope glycoproteins. By using this specific inhibitor of HIV entry, nucleolin, PHAP II, and PHAP I were identified as three V3 loop binding proteins (V3-BPs) implicated in the binding of HIV particles to CD4+ cells. Purified preparations of the V3-BPs, devoid of the CD4 and the fusin/CXCR4 cofactor, were able to inhibit infection of the CD4+ CEM cells by the lymphotropic HIV-1 Lai isolate. Recombinant gp120 was shown to bind the purified preparation of V3-BPs with a high affinity, and this binding was inhibited either by TASP or mAbs specific to the V3 loop. Consistent with the functional association of these proteins in the same complex, antibodies raised against any one of them inhibited HIV virion binding and infection of CD4+ cells (CEM, PBMC) by T lymphocyte- or macrophage-tropic, and as well as primary syncytium- or non-syncytium-inducing HIV-1 isolates.

CONCLUSION: Our results suggest that these three V3-BPs serve as a potential V3 loop receptor which plays an essential role in the binding of HIV particles to permissive cells. Consequently, the binding of HIV virions is coordinated by two complementary interactions, one through the CD4 and the other one through such a V3 loop receptor; both interactions being necessary before the membrane fusion event mediated by the chemokine receptors.

Keywords: AEGIS, Antigens, CD4, HIV-1, HIV Infections, CD4-Positive T-Lymphocytes, HIV-2, Receptors, CXCR4, Carrier Proteins, Virion, HIV Seropositivity, Membrane Fusion, Antibodies, Monoclonal, Proteins, Giant Cells, Pharmacokinetics, immunology, ICA12
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