Abstract
Upon detection of viral infections, cells activate the expression of type I interferons (IFNs) and pro-inflammatory cytokines to control viral dissemination. As part of their antiviral response, cells also trigger the translational shutoff response which prevents translation of viral mRNAs and cellular mRNAs in a non-selective manner. Intriguingly, mRNAs encoding for antiviral factors bypass this translational shutoff, suggesting the presence of additional regulatory mechanisms enabling expression of the self-defence genes. Here, we identified the dsRNA binding protein ILF3 as an essential host factor required for efficient translation of the central antiviral cytokine, IFNB1, and a subset of interferon-stimulated genes. By combining polysome profiling and next-generation sequencing, ILF3 was also found to be necessary to establish the dsRNA-induced transcriptional and translational programs. We propose a central role for the host factor ILF3 in enhancing expression of the antiviral defence mRNAs in cellular conditions where cap-dependent translation is compromised.
© The Author(s) 2019. Published by Oxford University Press on behalf of Nucleic Acids Research.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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A549 Cells
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Apoptosis Regulatory Proteins / genetics
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Apoptosis Regulatory Proteins / immunology
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Chemokine CCL5 / genetics
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Chemokine CCL5 / immunology
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Chemokine CXCL10 / genetics
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Chemokine CXCL10 / immunology
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Cytokines / genetics
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Cytokines / immunology
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DEAD Box Protein 58 / genetics
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DEAD Box Protein 58 / immunology
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Gene Expression Regulation
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HeLa Cells
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Host-Pathogen Interactions / genetics
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Host-Pathogen Interactions / immunology
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Humans
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Interferon-beta / genetics*
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Interferon-beta / immunology
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Intracellular Signaling Peptides and Proteins / genetics
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Intracellular Signaling Peptides and Proteins / immunology
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Nuclear Factor 90 Proteins / genetics*
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Nuclear Factor 90 Proteins / immunology
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Poly I-C / pharmacology
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Polyribosomes / drug effects
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Polyribosomes / genetics
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Polyribosomes / immunology
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Protein Biosynthesis*
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RNA, Double-Stranded / antagonists & inhibitors
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RNA, Double-Stranded / genetics*
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RNA, Double-Stranded / metabolism
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RNA, Messenger / genetics*
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RNA, Messenger / immunology
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RNA, Viral / antagonists & inhibitors
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RNA, Viral / genetics*
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RNA, Viral / metabolism
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RNA-Binding Proteins / genetics
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RNA-Binding Proteins / immunology
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Receptors, Immunologic
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Signal Transduction
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Ubiquitins / genetics
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Ubiquitins / immunology
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Virus Replication
Substances
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Apoptosis Regulatory Proteins
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CCL5 protein, human
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CXCL10 protein, human
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Chemokine CCL5
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Chemokine CXCL10
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Cytokines
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IFIT2 protein, human
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IFIT3 protein, human
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ILF3 protein, human
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Intracellular Signaling Peptides and Proteins
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Nuclear Factor 90 Proteins
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RNA, Double-Stranded
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RNA, Messenger
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RNA, Viral
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RNA-Binding Proteins
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Receptors, Immunologic
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Ubiquitins
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ISG15 protein, human
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Interferon-beta
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RIGI protein, human
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DEAD Box Protein 58
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Poly I-C