Browsing by Author "Da Costa Dias, Bianca"

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    A child with perinatal HIV infection and long-term sustained virological control following antiretroviral treatment cessation
    (Nature Research (part of Springer Nature), 2019) Violari, Avy; Cotton, Mark F.; Kuhn, Louise; Schramm, Diana B.; Paximadis, Maria; Loubser, Shayne; Shalekoff, Sharon; Da Costa Dias, Bianca; Otwombe, Kennedy; Liberty, Afaaf; McIntyre, James; Babiker, Abdel; Gibb, Diana; Tiemessen, Caroline T.
    ENGLISH ABSTRACT: Understanding HIV remission in rare individuals who initiated antiretroviral therapy (ART) soon after infection and then discontinued, may inform HIV cure interventions. Here we describe features of virus and host of a perinatally HIV-1 infected child with long-term sustained virological control. The child received early limited ART in the Children with HIV Early antiRetroviral therapy (CHER) trial. At age 9.5 years, diagnostic tests for HIV are negative and the child has characteristics similar to uninfected children that include a high CD4:CD8 ratio, low T cell activation and low CCR5 expression. Virus persistence (HIV-1 DNA and plasma RNA) is confirmed with sensitive methods, but replication-competent virus is not detected. The child has weak HIV-specific antibody and T cell responses. Furthermore, we determine his HLA and KIR genotypes. This case aids in understanding post-treatment control and may help design of future intervention strategies.
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    High resolution imaging study of interactions between the 37 kDa/67 kDa Laminin receptor and APP, beta-secretase and gamma-secretase in Alzheimer’s Disease
    (PLoS, 2014-06-27) Jovanovic, Katarina; Loos, Ben; Da Costa Dias, Bianca; Penny, Clement; Weiss, Stefan F. T.
    Alzheimer's disease (AD) is the most prevalent form of dementia affecting the elderly. Neurodegeneration is caused by the amyloid beta (Aβ) peptide which is generated from the sequential proteolytic cleavage of the Amyloid Precursor Protein (APP) by the β– and γ- secretases. Previous reports revealed that the 37 kDa/67 kDa laminin receptor (LRP/LR) is involved in APP processing, however, the exact mechanism by which this occurs remains largely unclear. This study sought to assess whether LRP/LR interacted with APP, β- or γ-secretase. Detailed confocal microscopy revealed that LRP/LR showed a strong co-localisation with APP, β- and γ-secretase, respectively, at various sub-cellular locations. Superresolution Structured Illumination Microscopy (SR-SIM) showed that interactions were unlikely between LRP/LR and APP and β-secretase, respectively, while there was strong co-localisation between LRP/LR and γ-secretase at this 80 nm resolution. FRET was further employed to assess the possibility of protein-protein interactions and only an interaction between LRP/LR and γ-secretase was found. FLAG co-immunoprecipitation confirmed these findings as LRP/LR co-immunoprecipitated with γ-secretase, but failed to do so with APP. These findings indicate that LRP/LR exerts its influence on Aβ shedding via a direct interaction with the γ-secretase and possibly an indirect interaction with the β-secretase.