Utilize este identificador para referenciar este registo: http://hdl.handle.net/10400.17/1702
Título: 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
Autor: Rocha, C
Calado, R
Borrego, P
Marcelino, JM
Bártolo, I
Rosado, L
Cavaco-Silva, P
Gomes, P
Família, C
Quintas, A
Skar, H
Leitner, T
Barroso, H
Taveira, N
Palavras-chave: HIV-2
Tropismo
Formação de Anticorpos
Criança
HDE HEM PED
Data: 2013
Editora: BioMed Central Ltd
Citação: Retrovirology. 2013, 10:110
Resumo: 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.
Peer review: Yes
URI: http://hdl.handle.net/10400.17/1702
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