ILF3 contributes to the establishment of the antiviral type I interferon program

• Published in: Nucleic acids research Vol. 48; no. 1; pp. 116 - 129
• Main Authors: Watson, Samir F, Bellora, Nicolas, Macias, Sara
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 10.01.2020
• Subjects: A549 Cells; Apoptosis Regulatory Proteins - genetics; Apoptosis Regulatory Proteins - immunology; Chemokine CCL5 - genetics; Chemokine CCL5 - immunology; Chemokine CXCL10 - genetics; Chemokine CXCL10 - immunology; Cytokines - genetics; Cytokines - immunology; DEAD Box Protein 58 - genetics; DEAD Box Protein 58 - immunology; Gene Expression Regulation; Gene regulation, Chromatin and Epigenetics; HeLa Cells; Host-Pathogen Interactions - genetics; Host-Pathogen Interactions - immunology; Humans; Interferon-beta - genetics; Interferon-beta - immunology; Intracellular Signaling Peptides and Proteins - genetics; Intracellular Signaling Peptides and Proteins - immunology; Nuclear Factor 90 Proteins - genetics; Nuclear Factor 90 Proteins - immunology; Poly I-C - pharmacology; Polyribosomes - drug effects; Polyribosomes - genetics; Polyribosomes - immunology; Protein Biosynthesis; Receptors, Immunologic; RNA, Double-Stranded - antagonists & inhibitors; RNA, Double-Stranded - genetics; RNA, Double-Stranded - metabolism; RNA, Messenger - genetics; RNA, Messenger - immunology; RNA, Viral - antagonists & inhibitors; RNA, Viral - genetics; RNA, Viral - metabolism; RNA-Binding Proteins - genetics; RNA-Binding Proteins - immunology; Signal Transduction; Ubiquitins - genetics; Ubiquitins - immunology; Virus Replication
• DOI: 10.1093/nar/gkz1060
• ISSN: 0305-1048

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.