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Evolution of the human immunodeficiency virus type 2 envelope in the first years of infection is associated with the dynamics of the neutralizing antibody response

2013Journal article Open access
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dc.contributor.authorRocha, Cheila
dc.contributor.authorCalado, Rita
dc.contributor.authorBorrego, Pedro
dc.contributor.authorMarcelino, José Maria
dc.contributor.authorBártolo, Inês
dc.contributor.authorRosado, Lino
dc.contributor.authorCavaco-Silva, Patrícia
dc.contributor.authorPerpétua, Gomes
dc.contributor.authorFamília, Carlos
dc.contributor.authorQuintas, Alexandre
dc.contributor.authorSkar, Helena
dc.contributor.authorLeitner, Thomas
dc.contributor.authorBarroso, Helena
dc.contributor.authorTaveira, Nuno
dc.date.accessioned2014-05-29T10:50:08Z
dc.date.available2014-05-29T10:50:08Z
dc.date.issued2013
dc.description.abstract"Background: Differently from HIV-1, HIV-2 disease progression usually takes decades without antiretroviral therapy and the majority of HIV-2 infected individuals survive as elite controllers with normal CD4+ T cell counts and low or undetectable plasma viral load. Neutralizing antibodies (Nabs) are thought to play a central role in HIV-2 evolution and pathogenesis. However, the dynamic of the Nab response and resulting HIV-2 escape during acute infection and their impact in HIV-2 evolution and disease progression remain largely unknown. Our objective was to characterize the Nab response and the molecular and phenotypic evolution of HIV-2 in association with Nab escape in the first years of infection in two children infected at birth. Results: CD4+ T cells decreased from about 50% to below 30% in both children in the first five years of infection and the infecting R5 viruses were replaced by X4 viruses within the same period. With antiretroviral therapy, viral load in child 1 decreased to undetectable levels and CD4+ T cells recovered to normal levels, which have been sustained at least until the age of 12. In contrast, viral load increased in child 2 and she progressed to AIDS and death at age 9. Beginning in the first year of life, child 1 raised high titers of antibodies that neutralized primary R5 isolates more effectively than X4 isolates, both autologous and heterologous. Child 2 raised a weak X4-specific Nab response that decreased sharply as disease progressed. Rate of evolution, nucleotide and amino acid diversity, and positive selection, were significantly higher in the envelope of child 1 compared to child 2. Rates of R5-to-X4 tropism switch, of V1 and V3 sequence diversification, and of convergence of V3 to a β-hairpin structure were related with rate of escape from the neutralizing antibodies. Conclusion: Our data suggests that the molecular and phenotypic evolution of the human immunodeficiency virus type 2 envelope are related with the dynamics of the neutralizing antibody response providing further support for a model in which Nabs play an important role in HIV-2 pathogenesis."por
dc.identifier.citationRetrovirology 2013, 10:110 doi:10.1186/1742-4690-10-110por
dc.identifier.issn1742-4690
dc.identifier.urihttp://hdl.handle.net/10400.26/6425
dc.language.isoengpor
dc.peerreviewedyespor
dc.publisherBioMed Centralpor
dc.relationMolecular epidemiology, drug resistance and pathogenesis of HIV and TB in Angola: the Angolan PErinatal HIV Cohort (APEHC)
dc.relation.publisherversionhttp://www.retrovirology.com/content/10/1/110por
dc.subjectVertical HIV-2 infectionpor
dc.subjectEvolution of the neutralizing antibody responsepor
dc.subjectEscape from neutralizationpor
dc.subjectMolecular evolutionpor
dc.subjectTropismpor
dc.titleEvolution of the human immunodeficiency virus type 2 envelope in the first years of infection is associated with the dynamics of the neutralizing antibody responsepor
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleMolecular epidemiology, drug resistance and pathogenesis of HIV and TB in Angola: the Angolan PErinatal HIV Cohort (APEHC)
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FSAU-FAR%2F115290%2F2009/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FSAU-EPI%2F122400%2F2010/PT
oaire.citation.startPage110por
oaire.citation.titleRetrovirologypor
oaire.citation.volume10por
oaire.fundingStream3599-PPCDT
oaire.fundingStream3599-PPCDT
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccesspor
rcaap.typearticlepor
relation.isProjectOfPublication15aded3d-70a1-4e02-8508-f5e6a4e56f9a
relation.isProjectOfPublicationc3b60260-41c1-4212-93cd-191d5b2e6133
relation.isProjectOfPublication.latestForDiscoveryc3b60260-41c1-4212-93cd-191d5b2e6133

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