Rocha, CheilaCalado, RitaBorrego, PedroMarcelino, José M.Bártolo, InêsRosado, LinoCavaco-Silva, PatríciaGomes, PerpétuaFamília, CarlosQuintas, AlexandreSkar, HelenaLeitner, ThomasBarroso, HelenaTaveira, Nuno2018-02-092018-02-092013-10-241742-4690PURE: 3601435PURE UUID: fcd62558-731e-4323-9a6b-af75b0947ef3Scopus: 84885972003PubMed: 24156513WOS: 000329043500002ORCID: /0000-0002-4597-1535/work/125367248http://www.scopus.com/inward/record.url?scp=84885972003&partnerID=8YFLogxKBackground: 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.1843355engEscape from neutralizationEvolution of the neutralizing antibody responseMolecular evolutionTropismVertical HIV-2 infectionVirologyInfectious DiseasesSDG 3 - Good Health and Well-beingjournal article10.1186/1742-4690-10-110https://www.scopus.com/pages/publications/84885972003