Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Blotting, Western
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Bronchi / immunology
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Bronchi / metabolism*
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Bronchi / virology
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Cells, Cultured
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DEAD Box Protein 58
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DEAD-box RNA Helicases / antagonists & inhibitors
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DEAD-box RNA Helicases / genetics
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DEAD-box RNA Helicases / metabolism*
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Epithelium / immunology
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Epithelium / metabolism*
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Epithelium / virology
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Female
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Fluorescent Antibody Technique
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HeLa Cells
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Humans
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Immunity, Innate
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Interferon-Induced Helicase, IFIH1
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Mice
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Mice, Knockout
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Picornaviridae Infections / immunology
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Picornaviridae Infections / metabolism*
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Picornaviridae Infections / virology
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RNA, Double-Stranded
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RNA, Messenger / genetics
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RNA, Small Interfering / genetics
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RNA, Viral / genetics
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Receptor, Interferon alpha-beta / physiology
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Receptors, Immunologic
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Reverse Transcriptase Polymerase Chain Reaction
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Rhinovirus / pathogenicity*
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Toll-Like Receptor 3 / antagonists & inhibitors
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Toll-Like Receptor 3 / genetics
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Toll-Like Receptor 3 / metabolism*
Substances
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Ifnar1 protein, mouse
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RNA, Double-Stranded
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RNA, Messenger
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RNA, Small Interfering
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RNA, Viral
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Receptors, Immunologic
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TLR3 protein, human
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Toll-Like Receptor 3
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Receptor, Interferon alpha-beta
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RIGI protein, human
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IFIH1 protein, human
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DEAD Box Protein 58
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DEAD-box RNA Helicases
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Interferon-Induced Helicase, IFIH1