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

Anna Gebhardt, Valter Bergant, Daniel Schnepf, Markus Moser, Arno Meiler, Dieudonnée Togbe, Claire MacKowiak, Line S. Reinert, Søren R. Paludan, Bernhard Ryffel, Alexey Stukalov, Peter Staeheli, Andreas Pichlmair

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

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.

Original languageEnglish
Article numbere1008155
JournalPLoS Pathogens
Volume15
Issue number12
DOIs
StatePublished - 2019

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