A fusion-intermediate state of HIV-1 gp41 targeted by broadly neutralizing antibodies.
Most antibodies induced by HIV-1 are ineffective at preventing initiation or spread of infection because they are either nonneutralizing or narrowly isolate-specific. Rare, "broadly neutralizing" antibodies have been detected that recognize relatively conserved regions on the envelope glycoprotein. Using stringently characterized, homogeneous preparations of trimeric HIV-1 envelope protein in relevant conformations, we have analyzed the molecular mechanism of neutralization by two of these antibodies, 2F5 and 4E10. We find that their epitopes, in the membrane-proximal segment of the envelope protein ectodomain, are exposed only on a form designed to mimic an intermediate state during viral entry. These results help explain the rarity of 2F5- and 4E10-like antibody responses and suggest a strategy for eliciting them.
Frey
Gary
G
Laboratory of Molecular Medicine, Children's Hospital, and Department of Pediatrics, Harvard Medical School, 320 Longwood Avenue, Boston, MA 02115, USA.
Peng
Hanqin
H
Rits-Volloch
Sophia
S
Morelli
Marco
M
Cheng
Yifan
Y
Chen
Bing
B
D000911:Antibodies, Monoclonal / Q000276:immunology; D001666:Binding Sites, Antibody; D015483:HIV Antibodies / Q000276:immunology*; D015488:HIV Antigens / Q000276:immunology; D015700:HIV Envelope Protein gp41 / Q000737:chemistry / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D007700:Kinetics; D008024:Ligands; D009500:Neutralization Tests; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000276:immunology*; D020349:Surface Plasmon Resonance; D054299:env Gene Products, Human Immunodeficiency Virus / Q000737:chemistry
D000911:Antibodies, Monoclonal; D015483:HIV Antibodies; D015488:HIV Antigens; D015700:HIV Envelope Protein gp41; D008024:Ligands; D011993:Recombinant Fusion Proteins; D054299:env Gene Products, Human Immunodeficiency Virus; C097729:gp140 envelope protein, Human immunodeficiency virus 1