Altered CD4 interactions of HIV type 1 LAI variants selected for the capacity to induce membrane fusion in the presence of a monoclonal antibody to domain 2 of CD4.

Important note: Information in this article was accurate in 1997. The state of the art may have changed since the publication date.

Altered CD4 interactions of HIV type 1 LAI variants selected for the capacity to induce membrane fusion in the presence of a monoclonal antibody to domain 2 of CD4.

AIDS Res Hum Retroviruses. 1996 Jul 20;12(11):1015-21. Unique Identifier : AIDSLINE MED/96424756
Klasse PJ; Sattentau QJ; Chester Beatty Laboratories, Institute of Cancer Research,; London, UK.

Abstract: 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.

Keywords: Antibodies, Monoclonal/*IMMUNOLOGY Antigens, CD4/IMMUNOLOGY/*METABOLISM Cell Line Cloning, Molecular Giant Cells/*VIROLOGY Human HIV Envelope Protein gp120/METABOLISM HIV Envelope Protein gp41/METABOLISM HIV-1/*METABOLISM *Membrane Fusion Neoplasm Proteins/*METABOLISM Support, Non-U.S. Gov't JOURNAL ARTICLE
970330
M9731496

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