NOVEL ANTI-CD4 MONOCLONAL-ANTIBODIES SEPARATE HUMAN-IMMUNODEFICIENCY-VIRUS INFECTION AND FUSION OF CD4+ CELLS FROM VIRUS BINDING

Human immunodeficiency virus (HIV) binds to cells via an interaction between C D 4 and the virus envelope glycoprotein, gpl20. Previous studies have localized the high affinity binding site for gpl20 to the first domain of C D 4, and monoclonal antibodies (mAbs) reactive with this region compete w i t h gpl20 binding and thereby block virus infectivity and syncytium formation. Despite a detailed understanding of the binding of gpl20 to C D 4, little is known of subsequent events leading to membrane fusion and virus entry. We describe two new mAbs reactive with the third domain of C D 4 that inhibit steps subsequent to virus binding critical for H I V infectivity and cell fusion. Binding of recombinant gpl20 or virus to C D 4 is not inhibited by these antibodies, whereas infection and syncytium formation by a number of H I V isolates are blocked. These findings demonstrate that in addition to virus binding, C D 4 may have an active role in membrane fusion. © 1990, Rockefeller University Press., All rights reserved.