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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
immunology and microbiology
Relationship of HIV-1 and SIV envelope glycoprotein trimer occupation and neutralization
Virology, Volume 377, No. 2, Year 2008
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Description
Insights into the process of HIV-1 neutralization may assist rational vaccine design. Here, we compared antibody neutralization against the JR-FL primary isolate and trimer binding affinities judged by native PAGE. Monovalent Fab-trimer binding and neutralization showed a direct quantitative relationship, implying that neutralization begins as each trimer is occupied by one antibody. At saturation, three Fab or soluble CD4 molecules engaged each trimer. In contrast, a maximum of one soluble CD4 molecule bound to functional SIV trimers with a truncated a gp41 tail. Remarkably, soluble CD4 was found to trigger dramatic enhancement of this virus. Unlike Fabs, a quantitative correlation between JR-FL trimer binding and neutralization was unclear for some, but not all IgGs, as neutralization was markedly increased, but trimer affinity was largely unchanged. In addition, only one molecule of certain gp41-specific IgGs appeared to be able to bind each trimer. We discuss the implications of these findings in weighing the relative contributions of size, multivalent binding and other possible effects of IgGs to explain their increased potency. © 2008 Elsevier Inc. All rights reserved.
Authors & Co-Authors
Crooks, Emma T.
United States, San Diego
Torrey Pines Institute for Molecular Studies
Jiang, Pengfei
United States, San Diego
Torrey Pines Institute for Molecular Studies
Franti, Michael
United States, Cambridge
Novartis Institutes for Biomedical Research, Inc.
Wong, Sharon
United States, San Diego
Torrey Pines Institute for Molecular Studies
Zwick, Michael B.
United States, San Diego
Scripps Research Institute
Hoxie, James A.
United States, Philadelphia
University of Pennsylvania
Robinson, James E.
United States, New Orleans
Tulane Medical Center
Moore, Penny L.
South Africa, Johannesburg
National Institute for Communicable Diseases
Binley, James M.
United States, San Diego
Torrey Pines Institute for Molecular Studies
Statistics
Citations: 47
Authors: 9
Affiliations: 6
Identifiers
Doi:
10.1016/j.virol.2008.04.045
ISSN:
00426822
e-ISSN:
10960341
Research Areas
Infectious Diseases
Study Approach
Qualitative
Quantitative