ADHESION MEDIATED BY INTERCELLULAR-ADHESION MOLECULE-1 ATTENUATES THEPOTENCY OF ANTIBODIES THAT BLOCK HIV-1 GP160-DEPENDENT SYNCYTIUM FORMATION

Several lines of evidence suggest that leukocyte adhesion molecules ca n promote HIV-1-mediated cell fusion and syncytium formation. In the p resent studies, the human kidney cell line, 293, was transfected with the envelope glycoprotein gene of the MN strain of HIV-I alone or cotr ansfected with a cDNA encoding intercellular adhesion molecule 1 (ICAM -1). It was found that 293 cells transfected with the HIV-1(MN)env gen e expressed the HIV-1 polyglycoprotein precursor, gp160, and the matur e gp120-gp41 complex. When mixed with a CD4(+) T cell line (CEM), the gp160-transfected cells mediated heterotypic cell fusion and formed mu ltinucleate syncytia. Virus-neutralizing monoclonal antibodies to the V2 and V3 domains of gp120 were able to inhibit syncytium formation, a s were monoclonal antibodies to CD4. When ICAM-1 was coexpressed with gp160, syncytium formation between the transfected kidney cells and un infected CD$(+) T cells was markedly enhanced. Inhibitors of HIV-1 inf ectivity (e.g., monoclonal antibodies to gp120, recombinant soluble CD 4) were able to prevent syncytium formation; however, the syncytium-bl ocking activity of these agents was significantly attenuated in cultur es in which ICAM-1 was cotransfected with gp160. These results confirm that leukocyte adhesion molecules can promote gp160-mediated syncytiu m formation and demonstrate, for the first time, that adhesive interac tions mediated by ICAM-1 and its contrareceptor, LFA-1, attenuate the syncytium-inhibiting activity of virus-neutralizing monoclonal antibod ies and soluble CD4. These findings suggest that the type and magnitud e of leukocyte adhesion molecules expressed on cells may be a signific ant variable in in vitro HIV-1 neutralization assays.