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
Origin: Repositório Comum
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."
