Publication
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
| dc.contributor.author | Rocha, C | |
| dc.contributor.author | Calado, R | |
| dc.contributor.author | Borrego, P | |
| dc.contributor.author | Marcelino, JM | |
| dc.contributor.author | Bártolo, I | |
| dc.contributor.author | Rosado, L | |
| dc.contributor.author | Cavaco-Silva, P | |
| dc.contributor.author | Gomes, P | |
| dc.contributor.author | Família, C | |
| dc.contributor.author | Quintas, A | |
| dc.contributor.author | Skar, H | |
| dc.contributor.author | Leitner, T | |
| dc.contributor.author | Barroso, H | |
| dc.contributor.author | Taveira, N | |
| dc.date.accessioned | 2014-03-05T16:50:16Z | |
| dc.date.available | 2014-03-05T16:50:16Z | |
| dc.date.issued | 2013 | |
| dc.description.abstract | 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. | por |
| dc.identifier.citation | Retrovirology. 2013, 10:110 | por |
| dc.identifier.uri | http://hdl.handle.net/10400.17/1702 | |
| dc.language.iso | eng | por |
| dc.peerreviewed | Yes | |
| dc.publisher | BioMed Central Ltd | por |
| dc.subject | HIV-2 | por |
| dc.subject | Tropismo | por |
| dc.subject | Formação de Anticorpos | por |
| dc.subject | Criança | por |
| dc.subject | HDE HEM PED | por |
| dc.title | 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 | por |
| dc.type | journal article | |
| dspace.entity.type | Publication | |
| oaire.citation.startPage | 110 | por |
| oaire.citation.volume | 10 | por |
| rcaap.rights | openAccess | por |
| rcaap.type | article | por |