The Journal of Immunology, Vol 150, Issue 1 290-301, Copyright © 1993 by American Association of Immunologists

ARTICLES

Ig CDR3-like region of the CD4 molecule is involved in HIV-induced syncytia formation but not in viral entry

P Corbeau, M Benkirane, R Weil, C David, S Emiliani, D Olive, C Mawas, A Serre and C Devaux
CRBM du CNRS, Centre de Tri des Molecules anti-HIV, Institut de Biologie, Montpellier, France.

The HIV1 envelope glycoprotein gp120 binding site has been previously mapped by genetic studies to the CDR2-like region of the first domain of the CD4 molecule. mAb reactive with epitopes linked to this region (e.g., OKT4A) inhibit both HIV entry into CD4-positive cells and syncytia formation. A second area of this domain, the CDR3-like region, has been shown to be involved in gp120-CD4 interactions, but its role remained so far unclear. We show here that a mAb specific for the CDR3- like region of the CD4 receptor, 13B8-2, actually blocks soluble gp120 binding to CD4, inhibits HIV-induced cell-cell fusion, and prevents viral production by infected cells. However, this mAb fails to inhibit the binding of viral particles to cell-surface CD4 and their entry into CD4-positive cells. These results strongly suggest i) that soluble gp120 and virion-anchored gp120 bind CD4 in distinct manners, ii) that gp120-CD4 interactions required for viral entry and syncytia formation are different, and iii) that mAb binding to the CDR3-like region of the first domain of CD4 affects a post-entry step of the HIV replicative cycle.

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