Limited neutralizing antibody specificities drive neutralization escape in early HIV-1 subtype C infection

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dc.contributor.authorMoore, Penny Len_ZA
dc.contributor.authorRanchobe, Nthabelengen_ZA
dc.contributor.authorLambson, Bronwen Een_ZA
dc.contributor.authorGray, Elin Sen_ZA
dc.contributor.authorCave, Eleanoren_ZA
dc.contributor.authorAbrahams, Melissa-Roseen_ZA
dc.contributor.authorBandawe, Gamaen_ZA
dc.contributor.authorMlisana, Kolekaen_ZA
dc.contributor.authorKarim, Salim S Abdoolen_ZA
dc.contributor.authorWilliamson, Carolynen_ZA
dc.date.accessioned2015-11-18T07:06:55Z
dc.date.available2015-11-18T07:06:55Z
dc.date.issued2009en_ZA
dc.description.abstractAuthor Summary Most HIV-1 infected individuals develop neutralizing antibodies against their own virus, termed an autologous neutralizing response. It is known that this response exerts pressure on the envelope of HIV, the target of such antibodies, resulting in neutralization escape. Here we have identified the targets of these antibodies and the precise genetic basis of neutralization escape in 4 individuals infected with HIV-1 subtype C. We show that V1V2 is commonly involved in escape, and that the C3 region is also a target in some cases. The latter observation confirms this region is exposed in subtype C, unlike subtype B. We show that neutralization escape is conferred by a few amino acid mutations, some of which are outside the antibody target site. Moreover, escape from these limited specificities even within a single individual occurs via a variety of different pathways involving substitutions, indels and glycan shifts. The finding in 2 individuals that an anti-C3 response developed first, followed by an anti-V1V2 response, suggests there may be specific regions of envelope particularly vulnerable to antibody neutralization. Overall, we propose a mechanistic explanation for how HIV-1 epitopes drive sequential waves of neutralization escape in early subtype C infection.en_ZA
dc.identifier.apacitationMoore, P. L., Ranchobe, N., Lambson, B. E., Gray, E. S., Cave, E., Abrahams, M., ... Williamson, C. (2009). Limited neutralizing antibody specificities drive neutralization escape in early HIV-1 subtype C infection. <i>PLoS One</i>, http://hdl.handle.net/11427/15119en_ZA
dc.identifier.chicagocitationMoore, Penny L, Nthabeleng Ranchobe, Bronwen E Lambson, Elin S Gray, Eleanor Cave, Melissa-Rose Abrahams, Gama Bandawe, Koleka Mlisana, Salim S Abdool Karim, and Carolyn Williamson "Limited neutralizing antibody specificities drive neutralization escape in early HIV-1 subtype C infection." <i>PLoS One</i> (2009) http://hdl.handle.net/11427/15119en_ZA
dc.identifier.citationMoore, P. L., Ranchobe, N., Lambson, B. E., Gray, E. S., Cave, E., Abrahams, M. R., ... & Morris, L. (2009). Limited neutralizing antibody specificities drive neutralization escape in early HIV-1 subtype C infection. PLoS Pathog, 5(9), e1000598. doi:10.1371/journal.ppat.1000598en_ZA
dc.identifier.ris TY - Journal Article AU - Moore, Penny L AU - Ranchobe, Nthabeleng AU - Lambson, Bronwen E AU - Gray, Elin S AU - Cave, Eleanor AU - Abrahams, Melissa-Rose AU - Bandawe, Gama AU - Mlisana, Koleka AU - Karim, Salim S Abdool AU - Williamson, Carolyn AB - Author Summary Most HIV-1 infected individuals develop neutralizing antibodies against their own virus, termed an autologous neutralizing response. It is known that this response exerts pressure on the envelope of HIV, the target of such antibodies, resulting in neutralization escape. Here we have identified the targets of these antibodies and the precise genetic basis of neutralization escape in 4 individuals infected with HIV-1 subtype C. We show that V1V2 is commonly involved in escape, and that the C3 region is also a target in some cases. The latter observation confirms this region is exposed in subtype C, unlike subtype B. We show that neutralization escape is conferred by a few amino acid mutations, some of which are outside the antibody target site. Moreover, escape from these limited specificities even within a single individual occurs via a variety of different pathways involving substitutions, indels and glycan shifts. The finding in 2 individuals that an anti-C3 response developed first, followed by an anti-V1V2 response, suggests there may be specific regions of envelope particularly vulnerable to antibody neutralization. Overall, we propose a mechanistic explanation for how HIV-1 epitopes drive sequential waves of neutralization escape in early subtype C infection. DA - 2009 DB - OpenUCT DO - 10.1371/journal.ppat.1000598 DP - University of Cape Town J1 - PLoS One LK - https://open.uct.ac.za PB - University of Cape Town PY - 2009 T1 - Limited neutralizing antibody specificities drive neutralization escape in early HIV-1 subtype C infection TI - Limited neutralizing antibody specificities drive neutralization escape in early HIV-1 subtype C infection UR - http://hdl.handle.net/11427/15119 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/15119
dc.identifier.urihttp://dx.doi.org/10.1371/journal.ppat.1000598
dc.identifier.vancouvercitationMoore PL, Ranchobe N, Lambson BE, Gray ES, Cave E, Abrahams M, et al. Limited neutralizing antibody specificities drive neutralization escape in early HIV-1 subtype C infection. PLoS One. 2009; http://hdl.handle.net/11427/15119.en_ZA
dc.language.isoengen_ZA
dc.publisherPublic Library of Scienceen_ZA
dc.publisher.departmentInstitute of Infectious Disease and Molecular Medicineen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rightsThis is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_ZA
dc.rights.holder© 2009 Moore et alen_ZA
dc.rights.urihttp://creativecommons.org/licenses/by/4.0en_ZA
dc.sourcePLoS Oneen_ZA
dc.source.urihttp://journals.plos.org/plospathogensen_ZA
dc.subject.otherCloningen_ZA
dc.subject.otherChemical neutralizationen_ZA
dc.subject.otherAntibodiesen_ZA
dc.subject.otherHIV-1en_ZA
dc.subject.otherAntibody responseen_ZA
dc.subject.otherViral loaden_ZA
dc.subject.otherAntibody specificityen_ZA
dc.subject.otherGlycosylationen_ZA
dc.titleLimited neutralizing antibody specificities drive neutralization escape in early HIV-1 subtype C infectionen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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