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dc.contributor.authorLacerda, Miguel
dc.contributor.authorMoore, Penny L
dc.contributor.authorNgandu, Nobubelo K
dc.contributor.authorSeaman, Michael
dc.contributor.authorGray, Elin S
dc.contributor.authorMurrell, Ben
dc.contributor.authorKrishnamoorthy, Mohan
dc.contributor.authorNonyane, Molati
dc.contributor.authorMadiga, Maphuti
dc.contributor.authorWibmer, Constantinos
dc.contributor.authorSheward, Daniel
dc.contributor.authorBailer, Robert T
dc.contributor.authorGao, Hongmei
dc.contributor.authorGreene, Kelli M
dc.contributor.authorKarim, Salim S
dc.contributor.authorMascola, John R
dc.contributor.authorKorber, Bette TM
dc.contributor.authorMontefiori, David C
dc.contributor.authorMorris, Lynn
dc.contributor.authorWilliamson, Carolyn
dc.contributor.authorSeoighe, Cathal
dc.contributor.author,
dc.date.accessioned2018-09-20T16:13:49Z
dc.date.available2018-09-20T16:13:49Z
dc.date.issued2013-01-01
dc.identifier.citationLacerda, Miguel; Moore, Penny L; Ngandu, Nobubelo K; Seaman, Michael; Gray, Elin S; Murrell, Ben; Krishnamoorthy, Mohan; Nonyane, Molati; Madiga, Maphuti; Wibmer, Constantinos; Sheward, Daniel; Bailer, Robert T; Gao, Hongmei; Greene, Kelli M; Karim, Salim S; Mascola, John R; Korber, Bette TM; Montefiori, David C; Morris, Lynn; Williamson, Carolyn; Seoighe, Cathal; , (2013). Identification of broadly neutralizing antibody epitopes in the hiv-1 envelope glycoprotein using evolutionary models. Virology Journal 10 ,
dc.identifier.issn1743-422X
dc.identifier.urihttp://hdl.handle.net/10379/12351
dc.description.abstractBackground: 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.
dc.publisherSpringer Nature
dc.relation.ispartofVirology Journal
dc.subjecthiv
dc.subjectantibodies
dc.subjectneutralization sensitivity
dc.subjectepitope prediction
dc.subjectevolutionary model
dc.subjectimmunodeficiency-virus type-1
dc.subjectb-cell responses
dc.subjectinfection
dc.subjectgp120
dc.subjectphylogenies
dc.subjectbinding
dc.subjectrecombination
dc.subjectindividuals
dc.subjectdiscovery
dc.subjectalgorithm
dc.titleIdentification of broadly neutralizing antibody epitopes in the hiv-1 envelope glycoprotein using evolutionary models
dc.typeArticle
dc.identifier.doi10.1186/1743-422x-10-347
dc.local.publishedsourcehttps://virologyj.biomedcentral.com/track/pdf/10.1186/1743-422X-10-347?site=virologyj.biomedcentral.com
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