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  • 1. Ellencrona, Karin
    et al.
    Syed, Asim
    Johansson, Magnus
    Flavivirus NS5 associates with host-cell proteins zonula occludens-1 (ZO-1) and regulating synaptic membrane exocytosis-2 (RIMS2) via an internal PDZ binding mechanism2009In: Biological chemistry (Print), ISSN 1431-6730, E-ISSN 1437-4315, Vol. 390, no 4, p. 319-323Article in journal (Refereed)
    Abstract [en]

    Dengue virus (DENV) and tick-borne encephalitis virus (TBEV) are flaviviruses, which can cause lethal hemorrhagic fever and encephalitis, respectively. Here, we demonstrate that the TBEV-NS5 and DENV-NS5 proteins use an internal binding mechanism to target human PDZ proteins. TBEV-NS5 has high affinity to regulating synaptic membrane exocytosis-2 (RIMS2) and Scribble, whereas DENV-NS5 binds primarily to the tight junction protein zonula occludens-1 (ZO-1). Targeting of TBEV-NS5 to the plasma membrane is stabilised by ZO-1; however, DENV-NS5 co-localises with ZO-1 in the nucleus. These interactions have potential important roles in the ability of flaviviruses to manipulate cell proliferation, junction permeability and the interferon pathways.

  • 2.
    Jacobsen, Marc
    et al.
    Max Planck Institute for Infection Biology, Department of Immunology, Berlin, Germany.
    Mattow, Jens
    Max Planck Institute for Infection Biology, Department of Immunology, Berlin, Germany; Department of Immunology, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany .
    Repsilber, Dirk
    Research Institute for the Biology of Farm Animals, Genetics and Biometry, Dummerstorf, Germany.
    Kaufmann, Stefan H E
    Max Planck Institute for Infection Biology, Department of Immunology, Berlin, Germany.
    Novel strategies to identify biomarkers in tuberculosis2008In: Biological chemistry (Print), ISSN 1431-6730, E-ISSN 1437-4315, Vol. 389, no 5, p. 487-95Article in journal (Refereed)
    Abstract [en]

    The more we learn about the immune response against tuberculosis (TB) and particularly about the features which distinguish protective immunity, disease susceptibility and pathology, the better we can define biomarkers which correlate with these different stages of infection. The most widely used biomarker in TB, which without a doubt is an important component of protective immunity, is IFNgamma secreted by antigen-specific CD4 T-cells. However, the complexity of the immune response against TB makes it more than likely that additional biomarkers are required for a reliable correlate of protection. As a corollary, we assume that a set of biomarkers will be required, termed a biosignature.

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