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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

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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, Patricia
dc.contributor.authorGomes, Perpetua
dc.contributor.authorFamilia, Carlos
dc.contributor.authorQuintas, Alexandre
dc.contributor.authorSkar, Helena
dc.contributor.authorLeitner, Thomas
dc.contributor.authorBarroso, Helena
dc.contributor.authorTaveira, Nuno
dc.date.accessioned2023-08-24T11:50:11Z
dc.date.available2023-08-24T11:50:11Z
dc.date.issued2013
dc.date.updated2023-02-03T14:30:58Z
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.pt_PT
dc.description.sponsorshipThis work was supported by grants PTDC/SAU-FAR/115290/2009 and PTDC/SAU-EPI/122400/2010 from Fundação para a Ciência e Tecnologia (FCT) (http://www.fct.pt), Portugal, a NIH grant (R01AI087520), and by Collaborative HIV and Anti-HIV Drug Resistance Network (CHAIN), from the European Union. Cheila Rocha, Rita Calado, Pedro Borrego and Inês Bártolo were supported by PhD scholarships from Fundação para a Ciência e Tecnologia, Portugal. Helena Skar was supported by a postdoctoral fellowship from the Swedish Research Council (623-2011-1100). The following reagents were obtained through the AIDS Research and Reference Reagent Program, Division of AIDS, NIAID, NIH: TZM-bl from Dr. John C. Kappes, Dr. Xiaoyun Wu and Tranzyme Inc.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationRocha C, Calado R, Borrego P, Marcelino JM, Bártolo I, Rosado L, et al. 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. Retrovirology [Internet]. 24 de outubro de 2013;10(1):110. Disponível em: https://doi.org/10.1186/1742-4690-10-110pt_PT
dc.identifier.doi10.1186/1742-4690-10-110pt_PT
dc.identifier.eid2-s2.0-84885972003
dc.identifier.slugcv-prod-1108458
dc.identifier.urihttp://hdl.handle.net/10451/58990
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherBioMed Centralpt_PT
dc.relationMolecular epidemiology, drug resistance and pathogenesis of HIV and TB in Angola: the Angolan PErinatal HIV Cohort (APEHC)
dc.relationCollaborative HIV and Anti-HIV Drug Resistance Network
dc.relation.publisherversionhttps://retrovirology.biomedcentral.com/articles/10.1186/1742-4690-10-110pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectVertical HIV-2 infectionpt_PT
dc.subjectEvolution of the neutralizing antibody responsept_PT
dc.subjectEscape from neutralizationpt_PT
dc.subjectMolecular evolutionpt_PT
dc.subjectTropismpt_PT
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 responsept_PT
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.awardTitleCollaborative HIV and Anti-HIV Drug Resistance Network
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.awardURIinfo:eu-repo/grantAgreement/EC/FP7/223131/EU
oaire.citation.issue1pt_PT
oaire.citation.startPage110pt_PT
oaire.citation.titleRetrovirologypt_PT
oaire.citation.volume10pt_PT
oaire.fundingStream3599-PPCDT
oaire.fundingStream3599-PPCDT
oaire.fundingStreamFP7
person.familyNameAlmeida Calado
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person.familyNameMARCELINO
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person.familyNameRodrigues Gomes Cavaco Silva
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person.givenNamePatricia
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person.givenNameCarlos
person.givenNameAlexandre
person.givenNameThomas
person.givenNameHelena
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project.funder.identifierhttp://doi.org/10.13039/501100001871
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project.funder.identifierhttp://doi.org/10.13039/501100008530
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameEuropean Commission
rcaap.cv.cienciaid661E-F5CB-F85A | Inês Bártolo
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