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

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


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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