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Sökning: WFRF:(Saudemont A)

  • Resultat 1-6 av 6
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  • 2019
  • Tidskriftsartikel (refereegranskat)
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  • Burman, Nathaniel, et al. (författare)
  • A virally-encoded tRNA neutralizes the PARIS antiviral defence system
  • Ingår i: Nature. - 0028-0836.
  • Tidskriftsartikel (refereegranskat)abstract
    • Viruses compete with each other for limited cellular resources, and some deliver defense mechanisms that protect the host from competing genetic parasites 1. PARIS is a defense system, often encoded in viral genomes, that is composed of a 55 kDa ABC ATPase (AriA) and a 35 kDa TOPRIM nuclease (AriB) 2. However, the mechanism by which AriA and AriB function in phage defense is unknown. Here we show that AriA and AriB assemble into a 425 kDa supramolecular immune complex. We use cryo-EM to determine the structure of this complex which explains how six molecules of AriA assemble into a propeller-shaped scaffold that coordinates three subunits of AriB. ATP-dependent detection of foreign proteins triggers the release of AriB, which assembles into a homodimeric nuclease that blocks infection by cleaving host tRNA Lys. Phage T5 subverts PARIS immunity through expression of a tRNA Lys variant that is not cleaved by PARIS, and thereby restores viral infection. Collectively, these data explain how AriA functions as an ATP-dependent sensor that detects viral proteins and activates the AriB toxin. PARIS is one of an emerging set of immune systems that form macromolecular complexes for the recognition of foreign proteins, rather than foreign nucleic acids 3.
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6.
  • Trzonkowski, Piotr, et al. (författare)
  • Hurdles in therapy with regulatory T cells
  • 2015
  • Ingår i: Science Translational Medicine. - : American Association for the Advancement of Science (AAAS). - 1946-6234 .- 1946-6242. ; 7:304
  • Tidskriftsartikel (refereegranskat)abstract
    • Improper activation of the immune system contributes to a variety of clinical conditions, including autoimmune and allergic diseases as well as solid organ and bone marrow transplantation. One approach to counteract this activation is through adoptive therapy with regulatory T cells (T-regs). Efforts to manufacture these cells have led to good maunfacturing practice-compliant protocols, and T-reg products are entering early clinical trials. Here, we report the stance of the European Union Cooperation in Science and Technology Action BM1305, "Action to Focus and Accelerate Cell-based Tolerance-inducing Therapies-A FACTT," which identifies hurdles hindering T-reg clinical applications in Europe and provides possible solutions.
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  • Resultat 1-6 av 6

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