tetano
Editor, Senior Moderator
PLoS Pathog. 2019 Dec 19;15(12):e1008155. doi: 10.1371/journal.ppat.1008155. [Epub ahead of print] [h=1]The alternative cap-binding complex is required for antiviral defense in vivo.[/h]
Gebhardt A[SUP]1,[/SUP][SUP]2[/SUP], Bergant V[SUP]1,[/SUP][SUP]2[/SUP], Schnepf D[SUP]3,[/SUP][SUP]4[/SUP], Moser M[SUP]5,[/SUP][SUP]6[/SUP], Meiler A[SUP]2[/SUP], Togbe D[SUP]7[/SUP], Mackowiak C[SUP]7[/SUP], Reinert L[SUP]8[/SUP], Paludan SR[SUP]8[/SUP], Ryffel B[SUP]7,[/SUP][SUP]9[/SUP], Stukalov A[SUP]1,[/SUP][SUP]2[/SUP], Staeheli P[SUP]3,[/SUP][SUP]10[/SUP], Pichlmair A[SUP]1,[/SUP][SUP]2,[/SUP][SUP]11[/SUP].
[h=3]Author information[/h] 1 Institute of Virology, Technical University of Munich, School of Medicine, Munich, Germany. 2 Innate Immunity Laboratory, Max-Planck Institute of Biochemistry, Martinsried, Germany. 3 Institute of Virology, University of Freiburg, Freiburg, Germany. 4 Spemann Graduate School of Biology and Medicine, Albert Ludwigs University Freiburg, Freiburg, Germany. 5 Department of Molecular Medicine, Max-Planck Institute of Biochemistry, Martinsried, Germany. 6 Center for Translational Cancer Research (TranslaTUM), TUM School of Medicine, Technical University of Munich, Munich, Germany. 7 INEM, Experimental Molecular Immunology, UMR7355 CNRS and University, Orleans, France. 8 Department of Biomedicine, University of Aarhus, Aarhus, Denmark. 9 Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa. 10 Faculty of Medicine, University of Freiburg, Freiburg, Germany. 11 German Center for Infection Research (DZIF), Munich partner site, Munich, Germany.
[h=3]Abstract[/h] 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.
PMID: 31856218 DOI: 10.1371/journal.ppat.1008155
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Gebhardt A[SUP]1,[/SUP][SUP]2[/SUP], Bergant V[SUP]1,[/SUP][SUP]2[/SUP], Schnepf D[SUP]3,[/SUP][SUP]4[/SUP], Moser M[SUP]5,[/SUP][SUP]6[/SUP], Meiler A[SUP]2[/SUP], Togbe D[SUP]7[/SUP], Mackowiak C[SUP]7[/SUP], Reinert L[SUP]8[/SUP], Paludan SR[SUP]8[/SUP], Ryffel B[SUP]7,[/SUP][SUP]9[/SUP], Stukalov A[SUP]1,[/SUP][SUP]2[/SUP], Staeheli P[SUP]3,[/SUP][SUP]10[/SUP], Pichlmair A[SUP]1,[/SUP][SUP]2,[/SUP][SUP]11[/SUP].
[h=3]Author information[/h] 1 Institute of Virology, Technical University of Munich, School of Medicine, Munich, Germany. 2 Innate Immunity Laboratory, Max-Planck Institute of Biochemistry, Martinsried, Germany. 3 Institute of Virology, University of Freiburg, Freiburg, Germany. 4 Spemann Graduate School of Biology and Medicine, Albert Ludwigs University Freiburg, Freiburg, Germany. 5 Department of Molecular Medicine, Max-Planck Institute of Biochemistry, Martinsried, Germany. 6 Center for Translational Cancer Research (TranslaTUM), TUM School of Medicine, Technical University of Munich, Munich, Germany. 7 INEM, Experimental Molecular Immunology, UMR7355 CNRS and University, Orleans, France. 8 Department of Biomedicine, University of Aarhus, Aarhus, Denmark. 9 Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa. 10 Faculty of Medicine, University of Freiburg, Freiburg, Germany. 11 German Center for Infection Research (DZIF), Munich partner site, Munich, Germany.
[h=3]Abstract[/h] 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.
PMID: 31856218 DOI: 10.1371/journal.ppat.1008155
Free full text