Potent Broad Cross-Neutralizing Sera Inhibit Attachment of Primary HIV-1 Isolates (Groups M and O) to Peripheral Blood Mononuclear Cells

Abstract

Gp160-directed antibody-mediated neutralization is thought to function by at least two different mechanisms that impair virus entry into the host cell: inhibition of virus attachment and inhibition of virus–cell membrane fusion. Previously, the neutralization spectra of sera derived from human immunodeficiency virus type 1 (HIV-1) infected patients were determined using 17 primary isolates belonging to HIV-1 group M (env clades A–H) and group O. The sera could be categorized as potent broad cross-neutralizing, limited cross-neutralizing, and nonneutralizing sera. The aim of this study was to examine whether the neutralizing capacity of polyclonal human sera correlates with their capacity to inhibit the attachment of infectious virions to the surface of peripheral blood mononuclear cells. A 100% correlation was found between the broad cross-neutralizing capacity and the ability to inhibit binding of primary isolates belonging to different genetic clades and groups to peripheral blood mononuclear cells. These results may indicate that broad cross-neutralizing antibodies are directed against those conserved regions on gp120 that interact with the cell receptor(s) and that those antibodies can therefore interfere with the binding of virus to the host cell.