Presence of antibodies to a putatively immunosuppressive part of human immunodeficiency virus (HIV) envelope glycoprotein gp41 is strongly associated with health among HIV-positive subjects.

Abstract

The IgG response to gp41 (envelope glycoprotein of Mr 41,000) of the human immunodeficiency virus (HIV) was studied with eight synthetic peptides derived from three different regions of the protein. We tested sera from 17 HIV-seronegative and 68 HIV-seropositive subjects in an enzyme immunoassay. No HIV antibody-negative serum reacted with any of the peptides. The peptide HIV-env 583-599 has a sequence similarity with immunosuppressive peptides derived from the transmembrane proteins of other retroviruses. Antibodies to this 17-mer (HIV-env 583-599; hereafter also referred to as pHIVIS, putative HIV immunosuppressive sequence) were detected in 27 of the 35 sera from healthy HIV-positive persons but only in 1 of the 33 sera from patients with HIV-related disease. Another 17-mer, displaced four amino acids N-terminally from pHIVIS, reacted with fewer of the sera from healthy seropositive subjects than pHIVIS but with no serum from healthy seropositive subjects than pHIVS but with no serum from ill seropositive patients. HIV-env 586-603, which shares two-thirds of its sequence with pHIVs, reacted with the sera from nearly all subjects, regardless of clinical status. The remaining five peptides did not discriminate between healthy and ill seropositive subjects either but gave lower reactivity rates. HIV-positive sera thus exhibited distinct patterns of reactivity with subsequences of gp41. We have mapped two overlapping epitopes within a narrow part of gp41; antibodies to the most N-terminally located of the two.sbd.i.e., the pHIVIS-reactive antibodies.sbd.might counteract a possible immunosuppressive effect of gp41.