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Resistance to antibody neutralization in HIV-2 infection occurs in late stage disease and is associated with X4 tropism

dc.contributor.authorMarcelino, José Maria
dc.contributor.authorBorrego, Pedro
dc.contributor.authorNilsson, Charlotta
dc.contributor.authorFamília, Carlos
dc.contributor.authorBarroso, Helena
dc.contributor.authorMaltez, Fernando
dc.contributor.authorDoroana, Manuela
dc.contributor.authorAntunes, Francisco
dc.contributor.authorQuintas, Alexandre
dc.contributor.authorTaveira, Nuno
dc.date.accessioned2013-11-25T09:54:53Z
dc.date.available2013-11-25T09:54:53Z
dc.date.issued2012-11-28
dc.descriptionThis is a non-final version of an article published in final form in AIDS. 28 November 2012 - Volume 26 - Issue 18 - p 2275–2284
dc.description.abstractObjectives: To characterize the nature and dynamics of the neutralizing antibody (NAb) response and escape in chronically HIV-2 infected patients.por
dc.description.abstractMethods: Twenty-eight chronically infected adults were studied over a period of 1-4 years. The neutralizing activity of plasma IgG antibodies against autologous and heterologous primary isolates was analyzed using a standard assay in TZM-bl cells. Coreceptor usage was determined in GHOST cells. The sequence and predicted 3Dstructure of the C2V3C3 Env region were determined for all isolates.por
dc.description.abstractResults: Only 50% of the patients consistently produced IgG NAbs to autologous and contemporaneous virus isolates. In contrast, 96% of the patients produced IgG antibodies that neutralized at least two isolates of a panel of six heterologous R5 isolates. Breadth and potency of the neutralizing antibodies were positively associated with the number of CD4+ T cells and with the titer and avidity of C2V3C3-specific binding IgG antibodies. X4 isolates were obtained only from late stage disease patients and were fully resistant to neutralization. The V3 loop of X4 viruses was longer, had a higher net charge and differed markedly in secondary structure compared to R5 viruses.por
dc.description.abstractConclusions: Most HIV-2 patients infected with R5 isolates produce C2V3C3-specific neutralizing antibodies whose potency and breadth decreases as the disease progresses. Resistance to antibody neutralization occurs in late stage disease and is usually associated with X4 viral tropism and major changes in V3 sequence and conformation. Our studies support a model of HIV-2 pathogenesis in which the neutralizing antibodies play a central role and have clear implications for the vaccine field.por
dc.description.sponsorshipFundação para a Ciência e Tecnologia, Portugalpor
dc.identifier.citationAIDS. 28 November 2012 - Volume 26 - Issue 18 - p 2275–2284por
dc.identifier.otherdoi: 10.1097/QAD.0b013e328359a89d
dc.identifier.urihttp://hdl.handle.net/10400.26/4941
dc.language.isoengpor
dc.peerreviewedyespor
dc.publisherLippincott Williams & Wilkinspor
dc.relation.publisherversionhttp://journals.lww.com/aidsonline/Abstract/2012/11280/Resistance_to_antibody_neutralization_in_HIV_2.2.aspxpor
dc.subjectHIV-2por
dc.subjectX4 Tropismpor
dc.subjectAntibody neutralizationpor
dc.titleResistance to antibody neutralization in HIV-2 infection occurs in late stage disease and is associated with X4 tropismpor
dc.typejournal article
dspace.entity.typePublication
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FSAU-FAR%2F115290%2F2009/PT
oaire.citation.endPage2284por
oaire.citation.startPage2275por
oaire.citation.titleAIDSpor
oaire.citation.volume26, n.º 18por
oaire.fundingStream3599-PPCDT
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccess
rcaap.typearticlepor
relation.isProjectOfPublication15aded3d-70a1-4e02-8508-f5e6a4e56f9a
relation.isProjectOfPublication.latestForDiscovery15aded3d-70a1-4e02-8508-f5e6a4e56f9a

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