Identification of broadly neutralizing antibody epitopes in the HIV-1 envelope glycoprotein using evolutionary models

 

Show simple item record

dc.contributor.author Lacerda, Miguel en_ZA
dc.contributor.author Moore, Penny en_ZA
dc.contributor.author Ngandu, Nobubelo en_ZA
dc.contributor.author Seaman, Michael en_ZA
dc.contributor.author Gray, Elin en_ZA
dc.contributor.author Murrell, Ben en_ZA
dc.contributor.author Krishnamoorthy, Mohan en_ZA
dc.contributor.author Nonyane, Molati en_ZA
dc.contributor.author Madiga, Maphuti en_ZA
dc.contributor.author Wibmer, Constantinos en_ZA
dc.contributor.author Sheward, Daniel en_ZA
dc.contributor.author Bailer, Robert en_ZA
dc.contributor.author Gao, Hongmei en_ZA
dc.contributor.author Greene, Kelli en_ZA
dc.contributor.author Karim, Salim S en_ZA
dc.contributor.author M en_ZA
dc.date.accessioned 2015-11-04T11:57:48Z
dc.date.available 2015-11-04T11:57:48Z
dc.date.issued 2013 en_ZA
dc.identifier.citation Lacerda, M., Moore, P. L., Ngandu, N. K., Seaman, M., Gray, E. S., Murrell, B., ... & CAVD-NSDP Consortium. (2013). Identification of broadly neutralizing antibody epitopes in the HIV-1 envelope glycoprotein using evolutionary models. Virol J, 10, 347. en_ZA
dc.identifier.uri http://hdl.handle.net/11427/14683
dc.identifier.uri http://dx.doi.org/10.1186/1743-422X-10-347
dc.description.abstract BACKGROUND:Identification of the epitopes targeted by antibodies that can neutralize diverse HIV-1 strains can provide important clues for the design of a preventative vaccine. METHODS: We have developed a computational approach that can identify key amino acids within the HIV-1 envelope glycoprotein that influence sensitivity to broadly cross-neutralizing antibodies. Given a sequence alignment and neutralization titers for a panel of viruses, the method works by fitting a phylogenetic model that allows the amino acid frequencies at each site to depend on neutralization sensitivities. Sites at which viral evolution influences neutralization sensitivity were identified using Bayes factors (BFs) to compare the fit of this model to that of a null model in which sequences evolved independently of antibody sensitivity. Conformational epitopes were identified with a Metropolis algorithm that searched for a cluster of sites with large Bayes factors on the tertiary structure of the viral envelope. RESULTS: We applied our method to ID50 neutralization data generated from seven HIV-1 subtype C serum samples with neutralization breadth that had been tested against a multi-clade panel of 225 pseudoviruses for which envelope sequences were also available. For each sample, between two and four sites were identified that were strongly associated with neutralization sensitivity (2ln(BF)>6), a subset of which were experimentally confirmed using site-directed mutagenesis. CONCLUSIONS: Our results provide strong support for the use of evolutionary models applied to cross-sectional viral neutralization data to identify the epitopes of serum antibodies that confer neutralization breadth. en_ZA
dc.language.iso eng en_ZA
dc.publisher BioMed Central Ltd en_ZA
dc.rights This is an Open Access article distributed under the terms of the Creative Commons Attribution License en_ZA
dc.rights.uri http://creativecommons.org/licenses/by/2.0 en_ZA
dc.source Virology Journal en_ZA
dc.source.uri http://www.virologyj.com/ en_ZA
dc.subject.other HIV en_ZA
dc.subject.other Antibodies en_ZA
dc.subject.other Neutralization sensitivity en_ZA
dc.subject.other Epitope prediction en_ZA
dc.subject.other Evolutionary model en_ZA
dc.title Identification of broadly neutralizing antibody epitopes in the HIV-1 envelope glycoprotein using evolutionary models en_ZA
dc.type Journal Article en_ZA
dc.rights.holder 2013 Lacerda et al.; licensee BioMed Central Ltd. en_ZA
uct.type.publication Research en_ZA
uct.type.resource Article en_ZA
dc.publisher.institution University of Cape Town
dc.publisher.faculty Faculty of Science en_ZA
dc.publisher.department Department of Statistical Sciences en_ZA
uct.type.filetype Text
uct.type.filetype Image


Files in this item

This item appears in the following Collection(s)

Show simple item record

This is an Open Access article distributed under the terms of the Creative Commons Attribution License Except where otherwise noted, this item's license is described as This is an Open Access article distributed under the terms of the Creative Commons Attribution License