title: Toll-like receptor-3 is dispensable for the innate microRNA response to West Nile virus (WNV).
abstract: The innate immune response to West Nile virus (WNV) infection involves recognition through toll-like receptors (TLRs) and RIG-I-like receptors (RLRs), leading to establishment of an antiviral state. MiRNAs (miRNAs) have been shown to be reliable biomarkers of TLR activation. Here, we sought to evaluate the contribution of TLR3 and miRNAs to the host response to WNV infection. We first analyzed HEK293-NULL and HEK293-TLR3 cells for changes in the innate immune response to infection. The presence of TLR3 did not seem to affect WNV load, infectivity or phosphorylation of IRF3. Analysis of experimentally validated NFκB-responsive genes revealed a WNV-induced signature largely independent of TLR3. Since miRNAs are involved in viral pathogenesis and the innate response to infection, we sought to identify changes in miRNA expression upon infection in the presence or absence of TLR3. MiRNA profiling revealed 70 miRNAs induced following WNV infection in a TLR3-independent manner. Further analysis of predicted gene targets of WNV signature miRNAs revealed genes highly associated with pathways regulating cell death, viral pathogenesis and immune cell trafficking.
authors.affiliation: Department of Microbiology and Immunology, Lineberger Comprehensive Cancer Center, Center for AIDS Research, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
authors.forename: Pauline E
authors.initials: PE
authors.lastname: Chugh
authors.affiliation: Department of Microbiology and Immunology, Lineberger Comprehensive Cancer Center, Center for AIDS Research, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
authors.forename: Blossom A
authors.initials: BA
authors.lastname: Damania
authors.affiliation: Department of Microbiology and Immunology, Lineberger Comprehensive Cancer Center, Center for AIDS Research, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
authors.forename: Dirk P
authors.initials: DP
authors.lastname: Dittmer
mesh_terms: D002460:Cell Line; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000378:metabolism; D020869:Gene Expression Profiling; D057809:HEK293 Cells; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology; D050838:Interferon Regulatory Factor-3 / Q000235:genetics / Q000378:metabolism*; D000072640:Interferon-Induced Helicase, IFIH1; D035683:MicroRNAs / Q000235:genetics / Q000276:immunology*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D011971:Receptors, Immunologic; D015398:Signal Transduction; D051196:Toll-Like Receptor 3 / Q000235:genetics / Q000378:metabolism*; D019562:Viral Load; D014901:West Nile Fever / Q000276:immunology; D014902:West Nile virus / Q000276:immunology*
chemical_list: C494232:IRF3 protein, human; D050838:Interferon Regulatory Factor-3; D035683:MicroRNAs; D016328:NF-kappa B; D012333:RNA, Messenger; D011971:Receptors, Immunologic; C495344:TLR3 protein, human; D051196:Toll-Like Receptor 3; C452820:RIGI protein, human; C452815:IFIH1 protein, human; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases; D000072640:Interferon-Induced Helicase, IFIH1