Modulation of primary human immunodeficiency virus type 1 envelope glycoprotein-mediated entry by human antibodies.
Recently, we and others have shown that the interaction between envelope specific antibodies and primary human immunodeficiency virus type 1 (HIV-1) isolates may result in either inhibition or enhancement of virus entry. The outcome proved to be determined by the virus isolate rather than by the specificity of the antiserum used. To study the mechanism underlying this phenomenon, a series of HIV-1 envelope glycoproteins from closely related primary virus isolates of different syncytium inducing phenotypes, together with chimeras of these proteins, were tested in an envelope trans-complementation assay for their sensitivity to either antibody mediated inhibition or enhancement of HIV-1 entry. Based on the observation that, in contrast to the inhibition of HIV-1 entry, antibody mediated enhancement was not temperature dependent and could not be mediated by F(ab) fragments, we concluded that the mechanisms underlying these phenomena are different and that antibody mediated enhancement of HIV-1 entry is largely if not exclusively mediated by HIV-1 glycoprotein cross-linking. The susceptibility of the envelope glycoprotein chimeric viruses to neutralization or enhancement of infectivity proved to be primarily determined by the configuration of the V3 loop, and the affinity of the antibodies to monomeric HIV-1 gp 160 molecules, proved to be of quantitative importance only. One human monoclonal antibody directed against gp41 (IAM 2F5) inhibited entry of all the viruses studied, irrespective of their phenotype, and directly proportional to its affinity to monomeric HIV-1 gp 160.
Schutten
M
M
Erasmus University Hospital Rotterdam, Institute of Virology, The Netherlands.
Andeweg
A C
AC
Rimmelzwaan
G F
GF
Osterhaus
A D
AD
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D019556:COS Cells; D003432:Cross-Linking Reagents; D015483:HIV Antibodies / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D015700:HIV Envelope Protein gp41 / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D010446:Peptide Fragments / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000276:immunology; D013696:Temperature; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D003432:Cross-Linking Reagents; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D015700:HIV Envelope Protein gp41; C059762:HIV envelope protein gp120 (305-321); D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins