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Neutralization and infectivity characteristics of envelope glycoproteins from human immunodeficiency virus type 1 infected donors whose sera exhibit broadly cross-reactive neutralizing activity

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dc.contributor.author Cham, F. en_US
dc.contributor.author Zhang, P. F. en_US
dc.contributor.author Heyndrickx, L. en_US
dc.contributor.author Bouma, P. en_US
dc.contributor.author Zhong, P. en_US
dc.contributor.author Katinger, H. en_US
dc.contributor.author Robinson, J. en_US
dc.contributor.author van der Groen, G. en_US
dc.contributor.author Quinnan, G. V. en_US
dc.date.accessioned 2007-12-06T14:46:39Z
dc.date.available 2007-12-06T14:46:39Z
dc.date.issued 2006 en_US
dc.identifier.doi http://dx.doi.org/10.1016/j.virol.2005.11.019
dc.identifier.other NOT AVAILABLE en_US
dc.identifier.other ITG-M1B en_US
dc.identifier.other ITG-M3A en_US
dc.identifier.other ITG-X8M en_US
dc.identifier.other MICRO en_US
dc.identifier.other U-VIROL en_US
dc.identifier.other JIF en_US
dc.identifier.other DOI en_US
dc.identifier.other ABSTRACT en_US
dc.identifier.uri http://hdl.handle.net/10390/1704
dc.description.abstract In this study, we tested the hypothesis that donors with broadly cross-reactive HIV-1 neutralizing (BCN) sera are infected with viruses encoding envelope glycoproteins (Envs) with unusual immunogenic properties. Cloned env genes were from samples of donors previously identified as having BCN antibodies (BCN donors) and from other donors not known to have such antibodies (non-BCN donors). Neutralization properties of viruses pseudotyped with BCN and non-BCN Envs were determined using BCN, non-BCN sera and broadly cross-neutralizing monoclonal antibodies (Mabs). BCN sera neutralized with higher frequency and geometric mean titers than non-BCN sera. Viruses pseudotyped with BCN Envs were mostly resistant to neutralization by anti-gp120 Mabs but tended to be more sensitive to the anti-gp41 Mabs, 2F5 and 4E10 than non-BCN Env-pseudotyped viruses. Sequence analysis of clones obtained from sequential samples of two BCN donors revealed respective 2F5 epitope mutations T662A and K665T. The K665T mutation evolved as the predominant genotype in the respective donor, consistent with an escape mutation event. The A662T mutation reduced sensitivity to 4E10, as well as 2F5 and homologous sera, consistent with neutralization escape mutation and targeting of the 2F5 epitope region by the serum. Our study suggests that viruses infecting these BCN donors encoded Envs that may have been unusually competent for induction of antibodies against the membrane proximal epitope region (MPER) of gp41, and these Envs may be useful vaccine components. en_US
dc.language English en_US
dc.subject Virology en_US
dc.subject HIV-1 env en_US
dc.subject Envelope en_US
dc.subject Glycoproteins en_US
dc.subject Neutralization en_US
dc.subject Immunodominant epitopes en_US
dc.subject Pseudovirions en_US
dc.subject Molecular sequence data en_US
dc.subject Amino acid sequences en_US
dc.subject Base sequence en_US
dc.subject Cross reactions en_US
dc.subject Point mutations en_US
dc.subject DNA en_US
dc.subject Genetic variation en_US
dc.title Neutralization and infectivity characteristics of envelope glycoproteins from human immunodeficiency virus type 1 infected donors whose sera exhibit broadly cross-reactive neutralizing activity en_US
dc.type Article en_US
dc.citation.issue 1 en_US
dc.citation.jtitle Virology en_US
dc.citation.volume 347 en_US
dc.citation.pages 36-51 en_US
dc.identifier.pmid http://www.ncbi.nlm.nih.gov/pubmed/16378633
dc.citation.jabbreviation Virology en_US


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