Author(s):
Rocha, Cheila ; Calado, Rita ; Borrego, Pedro ; Marcelino, José Maria ; Bártolo, Inês ; Rosado, Lino ; Cavaco-Silva, Patrícia ; Perpétua, Gomes ; Família, Carlos ; Quintas, Alexandre ; Skar, Helena ; Leitner, Thomas ; Barroso, Helena ; Taveira, Nuno
Date: 2013
Persistent ID: http://hdl.handle.net/10400.26/6425
Origin: Egas Moniz - Cooperativa de Ensino Superior, CRL
Project/scholarship:
info:eu-repo/grantAgreement/FCT/3599-PPCDT/115290/PT
;
info:eu-repo/grantAgreement/FCT/3599-PPCDT/122400/PT
;
Subject(s): Vertical HIV-2 infection; Evolution of the neutralizing antibody response; Escape from neutralization; Molecular evolution; Tropism
Description
"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."
