title: Human rhinovirus recognition in non-immune cells is mediated by Toll-like receptors and MDA-5, which trigger a synergetic pro-inflammatory immune response.
abstract: The early detection of invading viruses by the host depends on their identification by pathogen sensors. These include Toll-like receptors (TLRs) as well as cytoplasmic RNA helicases such as retinoic acid inducible protein I (RIG-I) and melanoma differentiation associated gene 5 (MDA-5). These pathogen sensors recognize specific molecular patterns found in viruses and trigger inflammatory and antiviral responses that result in the eradication of invading pathogens. In this study we investigated the specific recognition of Human rhinovirus 6 (HRV6) the common cold pathogen by the innate immune response in lung epithelial cells. Our experiments established that in the first stages on infection the TLRs play a crucial role in HRV recognition and that different constituents of HRV6 are recognized by different TLRs, while upon viral replication and generation of dsRNA the type I IFN inflammatory response is mediated by MDA-5. The HRV6 capsid is recognized via TLR2, whereas upon HRV6 ssRNA internalization the virus genome is recognized by TLR7 and TLR8. Upon generation of dsRNA the type I IFN response is mediated by MDA-5. The combined recognition by different TLRs and MDA5 and their upregulation concurs with the huge inflammatory response seen in the common cold caused by human rhinoviruses.
authors.affiliation: University of Sussex, Infection and Immunity Group, School of Life Sciences, Falmer, Brighton, UK. TriantafilouM@cardiff.ac.uk
authors.forename: Kathy
authors.initials: K
authors.lastname: Triantafilou
authors.forename: Emmanouil
authors.initials: E
authors.lastname: Vakakis
authors.forename: Edward A J
authors.initials: EA
authors.lastname: Richer
authors.forename: Gareth L
authors.initials: GL
authors.lastname: Evans
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Villiers
authors.forename: Martha
authors.initials: M
authors.lastname: Triantafilou
mesh_terms: D002460:Cell Line; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000276:immunology*; D004847:Epithelial Cells / Q000276:immunology* / Q000821:virology; D006801:Humans; D007113:Immunity, Innate; D007370:Interferon Type I / Q000276:immunology; D000072640:Interferon-Induced Helicase, IFIH1; D008168:Lung / Q000276:immunology / Q000821:virology; D010850:Picornaviridae Infections / Q000276:immunology* / Q000821:virology; D012229:Rhinovirus / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D051193:Toll-Like Receptors / Q000235:genetics / Q000276:immunology*
chemical_list: D007370:Interferon Type I; D051193:Toll-Like Receptors; C452815:IFIH1 protein, human; D053487:DEAD-box RNA Helicases; D000072640:Interferon-Induced Helicase, IFIH1