Two immunodominant domains of gp41 bind antibodies which enhance human immunodeficiency virus type 1 infection in vitro.
Four of eight human monoclonal antibodies (huMAbs) to gp41 were identified which could enhance human immunodeficiency virus type 1 (HIV-1) infection in vitro by complement-mediated antibody-dependent enhancement (C'-ADE). These enhancing huMAbs were mapped to two distinct domains on the HIV-1 gp41 transmembrane glycoprotein by using synthetic peptides. The first domain, amino acids 579 to 613 (peptide AA579-613), was recognized by three of the four enhancing huMAbs. The AA579-613 peptide blocked C'-ADE of HIV-1 infection in vitro whether it was mediated by these three huMAbs or by human polyclonal anti-HIV serum. The second domain, amino acids 644 to 663, bound the remaining enhancing huMAb. This peptide weakly blocked C'-ADE mediated by the huMAb and by an HIV immune globulin fraction but did not block C'-ADE mediated by a patient's serum. The patient's serum did react with the peptide in an enzyme immunoassay. The huMAbs to the two domains could interact in vitro to enhance HIV-1 infection in a synergistic manner. These two domains, which bind enhancing antibodies, are conserved between HIV-1 isolates as well as between HIV-2 and simian immunodeficiency virus isolates. These data demonstrate the existence of two conserved regions within the HIV-1 gp41 which bind enhancing antibodies; these two domains, amino acids 579 to 613 and 644 to 663, may prove important in HIV-1 vaccine development and in immunopathogenesis of HIV-1 infection.
Robinson
W E
WE
Department of Pathology, Vanderbilt University, Nashville, Tennessee 37232-2561.
Gorny
M K
MK
Xu
J Y
JY
Mitchell
W M
WM
Zolla-Pazner
S
S
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000276:immunology*; D001667:Binding, Competitive; D002460:Cell Line; D003165:Complement System Proteins / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D004797:Enzyme-Linked Immunosorbent Assay; D015483:HIV Antibodies / Q000276:immunology* / Q000378:metabolism; D015700:HIV Envelope Protein gp41 / Q000737:chemistry / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology* / Q000502:physiology; D006801:Humans; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology
D000911:Antibodies, Monoclonal; D015483:HIV Antibodies; D015700:HIV Envelope Protein gp41; D010446:Peptide Fragments; D003165:Complement System Proteins