Nature of nonfunctional envelope proteins on the surface of human immunodeficiency virus type 1.
Human immunodeficiency virus type 1 (HIV-1) neutralizing antibodies are thought be distinguished from nonneutralizing antibodies by their ability to recognize functional gp120/gp41 envelope glycoprotein (Env) trimers. The antibody responses induced by natural HIV-1 infection or by vaccine candidates tested to date consist largely of nonneutralizing antibodies. One might have expected a more vigorous neutralizing response, particularly against virus particles that bear functional trimers. The recent surprising observation that nonneutralizing antibodies can specifically capture HIV-1 may provide a clue relating to this paradox. Specifically, it was suggested that forms of Env, to which nonneutralizing antibodies can bind, exist on virus surfaces. Here, we present evidence that HIV-1 particles bear nonfunctional gp120/gp41 monomers and gp120-depleted gp41 stumps. Using a native electrophoresis band shift assay, we show that antibody-trimer binding predicts neutralization and that the nonfunctional forms of Env may account for virus capture by nonneutralizing antibodies. We hypothesize that these nonfunctional forms of Env on particle surfaces serve to divert the antibody response, helping the virus to evade neutralization.
Torrey Pines Institute for Molecular Studies, San Diego, CA 92121, USA.
Penny L
PL
Moore
Emma T
ET
Crooks
Lauren
L
Porter
Ping
P
Zhu
Charmagne S
CS
Cayanan
Henry
H
Grise
Paul
P
Corcoran
Michael B
MB
Zwick
Michael
M
Franti
Lynn
L
Morris
Kenneth H
KH
Roux
Dennis R
DR
Burton
James M
JM
Binley
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D015153:Blotting, Western; D004591:Electrophoresis, Polyacrylamide Gel; D024202:Electrophoretic Mobility Shift Assay; D004797:Enzyme-Linked Immunosorbent Assay; D015483:HIV Antibodies / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000276:immunology* / Q000502:physiology; D019302:HIV Envelope Protein gp160 / Q000737:chemistry / Q000276:immunology / Q000502:physiology; D015700:HIV Envelope Protein gp41 / Q000737:chemistry / Q000276:immunology* / Q000502:physiology; D015497:HIV-1 / Q000737:chemistry / Q000276:immunology* / Q000502:physiology; D006801:Humans; D051379:Mice; D016253:Microscopy, Immunoelectron; D009500:Neutralization Tests; D014771:Virion / Q000276:immunology
D000911:Antibodies, Monoclonal; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D019302:HIV Envelope Protein gp160; D015700:HIV Envelope Protein gp41