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We selected HIV-1-LAI variants with the ability to induce syncytium formation of C8166 cells in the presence of a monoclonal antibody (MAb), 5A8, to domain 2 of CD4. Five biologically cloned variants with at least 60-fold greater resistance than wild type to 5A8-mediated inhibition of syncytium formation were obtained. The variants exhibited reduced relative sensitivity to inhibition of syncytium formation and virus infection, not only by the selecting anti-domain 2 MAb, but also by MAbs to domains 1 and 3 of CD4. By contrast, the sensitivity of these variants to neutralization by soluble CD4 and bivalent CD4-IgG was greater than for the parental clone. The affinities of soluble CD4 for Env protein, in either solubilized or membrane-anchored form, did not differ significantly between the variants and LAI. Analyses of sCD4-induced exposure of the transmembrane protein at 4 and 37 degrees C suggested, however, that the variants had acquired an increased susceptibility to the triggering of conformational changes in their Env oligomers at 37 degrees C. This may represent a mechanism of both the increased resistance to the CD4 MAbs and the enhanced sensitivity to soluble CD4.

Original publication




Journal article


AIDS Res Hum Retroviruses

Publication Date





1015 - 1021


Antibodies, Monoclonal, CD4 Antigens, Cell Line, Cloning, Molecular, Giant Cells, HIV Envelope Protein gp120, HIV Envelope Protein gp41, HIV-1, Humans, Membrane Fusion, Neoplasm Proteins