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Browsing by Author "Correia, L."

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  • Gut disruption in HIV-2 infection despite reduced viremia
    Publication . Fernandes, S. M.; Pires, A. R.; Ferreira, C.; Tendeiro, R.; Correia, L.; Paulo, S. E.; Victorino, R. M.; Sousa, A. E.
    HIV-2 infection is highly prevalent inWest Africa and has been increasingly observed in non-African countries, mostly associated with migratory populations [1]. It has a much more benign course and lower viremia than HIV-1 [2], though with similar clinical spectra. Half of the HIV-2 infected patients with less than 200 CD4+ T-cells/ml exhibit undetectable viremia, despite harbouring numbers of infected cells comparable to their HIV-1 counterparts [3]. Moreover, CD4+ T-cell loss occurs in direct association with progressive immune activation in both infections, though the depletion rate is much slower in HIV-2 [2,4]. HIV-1 disease progression has been linked to disruption of gut-associated lymphoid tissue (GALT)and increased levels of microbial translocation, leading to systemic immune activation. There are currently no data on the impact of HIV-2 on GALT. Here, we provide evidence of HIV-2 replication in the gut despite the low viremia, which was associated with major mucosal disruption and CD4+ T-cell depletion that recovered upon antiretroviral treatment (ART).
    2014Journal article Restricted access Show more
  • HIV-2 infection is associated with preserved GALT homeostasis and epithelial integrity despite ongoing mucosal viral replication
    Publication . Fernandes, S. M.; Pires, A. R.; Matoso, P.; Ferreira, C.; Nunes-Cabaço, Helena; Correia, L.; Valadas, Emília; Poças, J.; Pacheco, P.; Veiga-Fernandes, Henrique; Foxall, Russell; Sousa, Ana E.
    The mechanisms that enable preservation of gut mucosal integrity during persistent viral replication and inherent inflammation remain unclear. Here, we investigated, for the first time, gut homeostasis in HIV-2 infection, a naturally occurring form of attenuated HIV disease. We found viral replication in both sigmoid and ileum of asymptomatic HIV-2+ patients (range: 240-851 circulating CD4+T-cells per μl) despite their undetectable viremia, accompanied by interferon-γ-producing CD8 T-cell expansion, irrespective of antiretroviral treatment. Nevertheless, there was no CD4 T-cell depletion, and Foxp3+ and IL-17- or IL-22-producing CD4 T-cell numbers were unaffected. Moreover, IL-22-producing innate lymphoid cells and IL-22-induced antimicrobial peptides and mucins were maintained. In agreement, the epithelium histology was preserved, including tight junction protein zonula occludens (ZO-1) levels. Furthermore, in vitro infection of colon epithelia with primary isolates revealed no HIV-2 impact on ZO-1 expression. Notably, sigmoid transcriptional levels of CCL20 and CCL28 were significantly increased, in direct correlation with GM-CSF, indicating a local response able to enhance CD4 T-cell recruitment. In conclusion, maintenance of mucosal integrity in HIV-2 infection was associated with T-cell recruitment responses, potentially counteracting CD4 T-cell depletion due to HIV-2 replication. These data have unique implications for the design of therapies targeting gut homeostasis in HIV-1 infection and other chronic inflammatory settings.
    2017Journal article Restricted access Show more
  • NF-kappa B and apoptosis in colorectal tumourigenesis
    Publication . Aranha, M. M.; Borralho, P. M.; Ravasco, P.; da Silva, I. B. Moreira; Correia, L.; Fernandes, A.; Camilo, M. E.; Rodrigues, C. M. P.
    Background Nuclear factor-kappa B (NF-kappa B) may play an important role in colorectal tumourigenesis, controlling cell cycle and apoptosis gene expression. In addition, imbalances between cell proliferation and cell death are thought to underlie neoplas
    2007Journal article Metadata only Show more