Co-ordinated role of TLR3, RIG-I and MDA5 in the innate response to rhinovirus in bronchial epithelium

• Published in: PLoS pathogens Vol. 6; no. 11; p. e1001178
• Main Authors: Slater, Louise, Bartlett, Nathan W, Haas, Jennifer J, Zhu, Jie, Message, Simon D, Walton, Ross P, Sykes, Annemarie, Dahdaleh, Samer, Clarke, Deborah L, Belvisi, Maria G, Kon, Onn M, Fujita, Takashi, Jeffery, Peter K, Johnston, Sebastian L, Edwards, Michael R
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.11.2010; Public Library of Science (PLoS)
• Subjects: Analysis; Animals; Blotting, Western; Bronchi - immunology; Bronchi - metabolism; Bronchi - virology; Cells, Cultured; Cellular signal transduction; Cytokines; DEAD Box Protein 58; DEAD-box RNA Helicases - antagonists & inhibitors; DEAD-box RNA Helicases - genetics; DEAD-box RNA Helicases - metabolism; Epithelium - immunology; Epithelium - metabolism; Epithelium - virology; Female; Fluorescent Antibody Technique; Gene expression; HeLa Cells; Humans; Immunity, Innate; Immunology/Cellular Microbiology and Pathogenesis; Immunology/Immunity to Infections; Immunology/Innate Immunity; Infectious Diseases/Respiratory Infections; Infectious Diseases/Viral Infections; Interferon-Induced Helicase, IFIH1; Kinases; Medical research; Mice; Mice, Knockout; Physiological aspects; Picornaviridae Infections - immunology; Picornaviridae Infections - metabolism; Picornaviridae Infections - virology; Proteins; Receptor, Interferon alpha-beta - physiology; Receptors, Immunologic; Respiratory tract diseases; Reverse Transcriptase Polymerase Chain Reaction; Rhinovirus; Rhinovirus - pathogenicity; Rhinoviruses; Risk factors; RNA, Double-Stranded; RNA, Messenger - genetics; RNA, Small Interfering - genetics; RNA, Viral - genetics; Toll-Like Receptor 3 - antagonists & inhibitors; Toll-Like Receptor 3 - genetics; Toll-Like Receptor 3 - metabolism; Toll-like receptors; Viral infections
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1001178

The relative roles of the endosomal TLR3/7/8 versus the intracellular RNA helicases RIG-I and MDA5 in viral infection is much debated. We investigated the roles of each pattern recognition receptor in rhinovirus infection using primary bronchial epithelial cells. TLR3 was constitutively expressed; however, RIG-I and MDA5 were inducible by 8-12 h following rhinovirus infection. Bronchial epithelial tissue from normal volunteers challenged with rhinovirus in vivo exhibited low levels of RIG-I and MDA5 that were increased at day 4 post infection. Inhibition of TLR3, RIG-I and MDA5 by siRNA reduced innate cytokine mRNA, and increased rhinovirus replication. Inhibition of TLR3 and TRIF using siRNA reduced rhinovirus induced RNA helicases. Furthermore, IFNAR1 deficient mice exhibited RIG-I and MDA5 induction early during RV1B infection in an interferon independent manner. Hence anti-viral defense within bronchial epithelium requires co-ordinated recognition of rhinovirus infection, initially via TLR3/TRIF and later via inducible RNA helicases.