Antibody neutralization and escape by HIV-1

Xiping Wei, Julie M. Decker, Shuyi Wang, Huxiong Hui, John C. Kappes, Xiaoyun Wu, Jesus F. Salazar-Gonzalez, Maria G. Salazar, J. Michael Kilby, Michael S. Saag, Natalia L. Komarova, Martin A. Nowak, Beatrice H. Hahn, Peter D. Kwong and George M. Shaw ()
Additional contact information
Xiping Wei: University of Alabama at Birmingham
Julie M. Decker: University of Alabama at Birmingham
Shuyi Wang: University of Alabama at Birmingham
Huxiong Hui: University of Alabama at Birmingham
John C. Kappes: University of Alabama at Birmingham
Xiaoyun Wu: University of Alabama at Birmingham
Jesus F. Salazar-Gonzalez: University of Alabama at Birmingham
Maria G. Salazar: University of Alabama at Birmingham
J. Michael Kilby: University of Alabama at Birmingham
Michael S. Saag: University of Alabama at Birmingham
Natalia L. Komarova: Institute for Advanced Study
Martin A. Nowak: Institute for Advanced Study
Beatrice H. Hahn: University of Alabama at Birmingham
Peter D. Kwong: Vaccine Research Center, National Institutes of Health
George M. Shaw: University of Alabama at Birmingham

Nature, 2003, vol. 422, issue 6929, 307-312

Abstract: Abstract Neutralizing antibodies (Nab) are a principal component of an effective human immune response to many pathogens, yet their role in HIV-1 infection is unclear1,2,3,4,5,6. To gain a better understanding of this role, we examined plasma from patients with acute HIV infection. Here we report the detection of autologous Nab as early as 52 days after detection of HIV-specific antibodies. The viral inhibitory activity of Nab resulted in complete replacement of neutralization-sensitive virus by successive populations of resistant virus. Escape virus contained mutations in the env gene that were unexpectedly sparse, did not map generally to known neutralization epitopes, and involved primarily changes in N-linked glycosylation. This pattern of escape, and the exceptional density of HIV-1 envelope glycosylation generally7,8, led us to postulate an evolving ‘glycan shield’ mechanism of neutralization escape whereby selected changes in glycan packing prevent Nab binding but not receptor binding. Direct support for this model was obtained by mutational substitution showing that Nab-selected alterations in glycosylation conferred escape from both autologous antibody and epitope-specific monoclonal antibodies. The evolving glycan shield thus represents a new mechanism contributing to HIV-1 persistence in the face of an evolving antibody repertoire.

Date: 2003
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DOI: 10.1038/nature01470

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