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Journal of Virology, March 2006, p. 2515-2528, Vol. 80, No. 5
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.5.2515-2528.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Nature of Nonfunctional Envelope Proteins on the Surface of Human Immunodeficiency Virus Type 1

Penny L. Moore,1,2 Emma T. Crooks,1 Lauren Porter,3 Ping Zhu,3 Charmagne S. Cayanan,4,{dagger} Henry Grise,3 Paul Corcoran,1 Michael B. Zwick,4 Michael Franti,5 Lynn Morris,2 Kenneth H. Roux,3 Dennis R. Burton,4 and James M. Binley1,4*

Torrey Pines Institute for Molecular Studies, 3550 General Atomics Court, San Diego, California 92121,1 National Institute for Communicable Diseases, Sandringham, Johannesburg, South Africa,2 Department of Biological Science and Institute of Molecular Biophysics, Florida State University, Tallahassee, Florida 32306,3 Departments of Immunology and Molecular Biology, The Scripps Research Institute, La Jolla, California 92037,4 Progenics Pharmaceuticals, Inc., Tarrytown, New York 105915

Received 19 September 2005/ Accepted 5 December 2005

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.

* Corresponding author. Mailing address: Torrey Pines Institute for Molecular Studies, 3550 General Atomics Court, San Diego, CA 92121. Phone: (858) 909 5142. Fax: (858) 455 3804. E-mail: jbinley{at}tpims.org.

{dagger} Present address: Kalypsys, Inc., 10420 Wateridge Circle, San Diego, CA 92121.

Journal of Virology, March 2006, p. 2515-2528, Vol. 80, No. 5
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.5.2515-2528.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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