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Glycans flanking the hypervariable connecting peptide between the a and B strands of the V1/V2 domain of HIV-1 gp120 confer resistance to antibodies that neutralize CRF01-AE viruses

dc.contributor.authorSara M. O'Rourkeen_US
dc.contributor.authorRuengpung Sutthenten_US
dc.contributor.authorPham Phungen_US
dc.contributor.authorKathryn A. Mesaen_US
dc.contributor.authorNormand L. Frigonen_US
dc.contributor.authorBriana Toen_US
dc.contributor.authorNavin Horthongkhamen_US
dc.contributor.authorKay Limolien_US
dc.contributor.authorTerri Wrinen_US
dc.contributor.authorPhillip W. Bermanen_US
dc.contributor.otherUniversity of California, Santa Cruzen_US
dc.contributor.otherMahidol Universityen_US
dc.contributor.otherMonogram Biosciencesen_US
dc.contributor.otherGladstone Institute of Virology and Immunologyen_US
dc.date.accessioned2018-11-23T09:32:00Z
dc.date.available2018-11-23T09:32:00Z
dc.date.issued2015-03-20en_US
dc.description.abstract© 2015 O'Rourke et al. Understanding the molecular determinants of sensitivity and resistance to neutralizing antibodies is critical for the development of vaccines designed to prevent HIV infection. In this study, we used a genetic approach to characterize naturally occurring polymorphisms in the HIV envelope protein that conferred neutralization sensitivity or resistance. Libraries of closely related envelope genes, derived from virus quasi-species, were constructed from individuals infected with CRF01-AE viruses. The libraries were screened with plasma containing broadly neutralizing antibodies, and neutralization sensitive and resistant variants were selected for sequence analysis. In vitro mutagenesis allowed us to identify single amino acid changes in three individuals that conferred resistance to neutralization by these antibodies. All three mutations created N-linked glycosylation sites (two at N136 and one at N149) proximal to the hypervariable connecting peptide between the C-terminus of the A strand and the N-terminus of the B strand in the four-stranded V1/V2 domain β-sheet structure. Although N136 has previously been implicated in the binding of broadly neutralizing monoclonal antibodies, this glycosylation site appears to inhibit the binding of neutralizing antibodies in plasma from HIV-1 infected subjects. Previous studies have reported that the length of the V1/V2 domain in transmitted founder viruses is shorter and possesses fewer glycosylation sites compared to viruses isolated from chronic infections. Our results suggest that vaccine immunogens based on recombinant envelope proteins from clade CRF01-AE viruses might be improved by inclusion of envelope proteins that lack these glycosylation sites. This strategy might improve the efficacy of the vaccines used in the partiallyen_US
dc.identifier.citationPLoS ONE. Vol.10, No.3 (2015)en_US
dc.identifier.doi10.1371/journal.pone.0119608en_US
dc.identifier.issn19326203en_US
dc.identifier.other2-s2.0-84925967803en_US
dc.identifier.urihttps://repository.li.mahidol.ac.th/handle/20.500.14594/35192
dc.rightsMahidol Universityen_US
dc.rights.holderSCOPUSen_US
dc.source.urihttps://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84925967803&origin=inwarden_US
dc.subjectAgricultural and Biological Sciencesen_US
dc.subjectBiochemistry, Genetics and Molecular Biologyen_US
dc.subjectMedicineen_US
dc.titleGlycans flanking the hypervariable connecting peptide between the a and B strands of the V1/V2 domain of HIV-1 gp120 confer resistance to antibodies that neutralize CRF01-AE virusesen_US
dc.typeArticleen_US
dspace.entity.typePublication
mu.datasource.scopushttps://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84925967803&origin=inwarden_US

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