The alternative cap-binding complex is required for antiviral defense in vivo

English version

Autoři: Anna Gebhardt ^aff001; Valter Bergant ^aff001; Daniel Schnepf ^aff003; Markus Moser ^aff005; Arno Meiler ^aff002; Dieudonnée Togbe ^aff007; Claire Mackowiak ^aff007; Line Reinert ^aff008; Søren R. Paludan ^aff008; Bernhard Ryffel ^aff007; Alexey Stukalov ^aff001; Peter Staeheli ^aff003; Andreas Pichlmair ^aff001
Působiště autorů: Institute of Virology, Technical University of Munich, School of Medicine, Munich, Germany ^aff001; Innate Immunity Laboratory, Max-Planck Institute of Biochemistry, Martinsried, Germany ^aff002; Institute of Virology, University of Freiburg, Freiburg, Germany ^aff003; Spemann Graduate School of Biology and Medicine, Albert Ludwigs University Freiburg, Freiburg, Germany ^aff004; Department of Molecular Medicine, Max-Planck Institute of Biochemistry, Martinsried, Germany ^aff005; Center for Translational Cancer Research (TranslaTUM), TUM School of Medicine, Technical University of Munich, Munich, Germany ^aff006; INEM, Experimental Molecular Immunology, UMR7355 CNRS and University, Orleans, France ^aff007; Department of Biomedicine, University of Aarhus, Aarhus, Denmark ^aff008; Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa ^aff009; Faculty of Medicine, University of Freiburg, Freiburg, Germany ^aff010; German Center for Infection Research (DZIF), Munich partner site, Munich, Germany ^aff011
Vyšlo v časopise: The alternative cap-binding complex is required for antiviral defense in vivo. PLoS Pathog 15(12): e32767. doi:10.1371/journal.ppat.1008155
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.ppat.1008155

Souhrn

Cellular response to environmental challenges requires immediate and precise regulation of transcriptional programs. During viral infections, this includes the expression of antiviral genes that are essential to combat the pathogen. Transcribed mRNAs are bound and escorted to the cytoplasm by the cap-binding complex (CBC). We recently identified a protein complex consisting of NCBP1 and NCBP3 that, under physiological conditions, has redundant function to the canonical CBC, consisting of NCBP1 and NCBP2. Here, we provide evidence that NCBP3 is essential to mount a precise and appropriate antiviral response. Ncbp3-deficient cells allow higher virus growth and elicit a reduced antiviral response, a defect happening on post-transcriptional level. Ncbp3-deficient mice suffered from severe lung pathology and increased morbidity after influenza A virus challenge. While NCBP3 appeared to be particularly important during viral infections, it may be more broadly involved to ensure proper protein expression.

Klíčová slova:

Antiviral immune response – Cytokines – Immune response – Influenza A virus – Messenger RNA – Small interfering RNAs – Viral replication – Vesicular stomatitis virus

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