Browsing by Author "Rocha, Cheila"
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- Baseline susceptibility of primary HIV-2 to entry inhibitorsPublication . Borrego, Pedro; Calado, Rita; Marcelino, José M; Bártolo, Inês; Rocha, Cheila; Cavaco-Silva, Patrícia; Doroana, Manuela; Antunes, Francisco; Maltez, Fernando; Caixas, Umbelina; Barroso, Helena; Taveira, NunoBackground: The baseline susceptibility of primary HIV-2 to maraviroc (MVC) and other entry inhibitors is currently unknown.
- Development of synthetic light-chain antibodies as novel and potent HIV fusion inhibitorsPublication . Cunha-Santos, Catarina; Figueira, Tiago N.; Borrego, Pedro; Oliveira, Soraia S.; Rocha, Cheila; Couto, Andreia; Cantante, Cátia; Santos- Costa, Quirina; Azevedo-Pereira, José M.; Fontes, Carlos M. G. A.; Taveira, Nuno; Aires-Da-Silva, Frederico; Castanho, Miguel A. R. B.; Veiga, Ana Salomé; Gonçalves, João"Objective: To develop a novel and potent fusion inhibitor of HIV infection based on a rational strategy for synthetic antibody library construction. Design: The reduced molecular weight of single-domain antibodies (sdAbs) allows targeting of cryptic epitopes, the most conserved and critical ones in the context of HIV entry. Heavy-chain sdAbs from camelids are particularly suited for this type of epitope recognition because of the presence of long and flexible antigen-binding regions [complementary-determining regions (CDRs)]."
- Evolution of the human immunodeficiency virus type 2 envelope in the first years of infection is associated with the dynamics of the neutralizing antibody responsePublication . 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"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."
- Potency of HIV-2-specific antibodies increase in direct association with loss of memory B cellsPublication . Rocha, Cheila; Duarte, Joana; Borrego, Pedro; Calado, Rita; Marcelino, José Maria; Tendeiro, Rita; Valadas, Emília; Sousa, Ana Espada; Taveira, NunoPotent HIV-neutralizing antibodies are critical for vaccination and viral reservoir control. High levels of neutralizing antibodies characterize HIV-2 infection, a naturally occurring model of attenuated HIV disease with low-to-undectable viremia. We found that HIV-2-specific antibody potency increased in direct association with the loss of both switched and unswitched memory B cells in untreated HIV-2 infection. Thus, HIV antibody affinity maturation is linked to memory B-cell exhaustion even in reduced viremia settings.