Antibody neutralization and escape by HIV-1.

@article{citeulike:2049448, 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 unclear. 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 generally, 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.}, address = {Howard Hughes Medical Institute, University of Alabama at Birmingham, 720 South 20th Street, KAUL 816, Birmingham, Alabama 35294-0024, USA.}, author = {Wei, X. and Decker, J. M. and Wang, S. and Hui, H. and Kappes, J. C. and Wu, X. and Salazar-Gonzalez, J. F. and Salazar, M. G. and Kilby, J. M. and Saag, M. S. and Komarova, N. L. and Nowak, M. A. and Hahn, B. H. and Kwong, P. D. and Shaw, G. M. }, citeulike-article-id = {2049448}, doi = {http://dx.doi.org/10.1038/nature01470}, issn = {0028-0836}, journal = {Nature}, keywords = {antibody, evolution, hiv}, month = {March}, number = {6929}, pages = {307--312}, posted-at = {2007-12-03 12:19:11}, priority = {5}, title = {Antibody neutralization and escape by HIV-1.}, url = {http://dx.doi.org/10.1038/nature01470}, volume = {422}, year = {2003} }

TY - JOUR ID - citeulike:2049448 L3 - citeulike-article-id:2049448 TI - Antibody neutralization and escape by HIV-1. JF - Nature VL - 422 IS - 6929 SP - 307 EP - 312 AD - Howard Hughes Medical Institute, University of Alabama at Birmingham, 720 South 20th Street, KAUL 816, Birmingham, Alabama 35294-0024, USA. SN - 0028-0836 N2 - Neutralizing antibodies (Nab) are a principal component of an effective human immune response to many pathogens, yet their role in HIV-1 infection is unclear. 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 generally, 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. KW - antibody KW - evolution KW - hiv AU - Wei, X AU - Decker, JM AU - Wang, S AU - Hui, H AU - Kappes, JC AU - Wu, X AU - Salazar-Gonzalez, JF AU - Salazar, MG AU - Kilby, JM AU - Saag, MS AU - Komarova, NL AU - Nowak, MA AU - Hahn, BH AU - Kwong, PD AU - Shaw, GM PY - 2003/03/20/ UR - http://dx.doi.org/10.1038/nature01470 ER -