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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

2013-10-24Artigo científico Acesso aberto
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dc.contributor.authorRocha, Cheila
dc.contributor.authorCalado, Rita
dc.contributor.authorBorrego, Pedro
dc.contributor.authorMarcelino, José M.
dc.contributor.authorBártolo, Inês
dc.contributor.authorRosado, Lino
dc.contributor.authorCavaco-Silva, Patrícia
dc.contributor.authorGomes, Perpétua
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.contributor.institutionInstituto de Higiene e Medicina Tropical (IHMT)
dc.contributor.institutionCentro de Malária e outras Doenças Tropicais (CMDT)
dc.contributor.pblBioMed Central (BMC)
dc.date.accessioned2018-02-09T23:10:19Z
dc.date.available2018-02-09T23:10:19Z
dc.date.issued2013-10-24
dc.description.abstractBackground: 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.en
dc.description.versionpublishersversion
dc.description.versionpublished
dc.format.extent1843355
dc.identifier.doi10.1186/1742-4690-10-110
dc.identifier.issn1742-4690
dc.identifier.otherPURE: 3601435
dc.identifier.otherPURE UUID: fcd62558-731e-4323-9a6b-af75b0947ef3
dc.identifier.otherScopus: 84885972003
dc.identifier.otherPubMed: 24156513
dc.identifier.otherWOS: 000329043500002
dc.identifier.otherORCID: /0000-0002-4597-1535/work/125367248
dc.identifier.urihttp://www.scopus.com/inward/record.url?scp=84885972003&partnerID=8YFLogxK
dc.identifier.urlhttps://www.scopus.com/pages/publications/84885972003
dc.language.isoeng
dc.peerreviewedyes
dc.subjectEscape from neutralization
dc.subjectEvolution of the neutralizing antibody response
dc.subjectMolecular evolution
dc.subjectTropism
dc.subjectVertical HIV-2 infection
dc.subjectVirology
dc.subjectInfectious Diseases
dc.subjectSDG 3 - Good Health and Well-being
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 responseen
dc.typejournal article
degois.publication.issue1
degois.publication.titleRetrovirology
degois.publication.volume10
dspace.entity.typePublication
rcaap.rightsopenAccess

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