title: DHX15 senses double-stranded RNA in myeloid dendritic cells.
abstract: Many members of the DEXD/H box helicase family play important roles in the innate immune system against viral infection. Therefore, we isolated dsRNA complex in myeloid dendritic cells. We found that DHx15, a DEXDc helicase family member, is one of the components of this complex. Knockdown of DHX15 expression by short hairpin RNA efficiently reduced the ability of myeloid dendritic cells to produce IFN-β, IL-6, and TNF-α in response to dsRNA and RNA virus. DHX15 specifically bound polyinosine-polycytidylic acid via its helicase C-terminal domain. DHX15 interacted with MAVS and formed a complex following stimulation with polyinosine-polycytidylic acid. The N-terminal domain containing a DEXDc motif in DHX15 bound the C terminus of MAVS. DHX15 is required to activate IRF3 phosphorylation as well as NF-κB and MAPK signaling during RNA virus infection. We, therefore, identified DHX15 as a new RNA virus sensor mediated by MAVS to activate the immune responses to RNA.
authors.affiliation: Baylor Institute for Immunology Research, Baylor Research Institute, Dallas, TX 75204; and.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Lu
authors.affiliation: Baylor Institute for Immunology Research, Baylor Research Institute, Dallas, TX 75204; and.
authors.forename: Ning
authors.initials: N
authors.lastname: Lu
authors.affiliation: Baylor Institute for Immunology Research, Baylor Research Institute, Dallas, TX 75204; and.
authors.forename: Leiyun
authors.initials: L
authors.lastname: Weng
authors.affiliation: Immunobiology and Transplant Research, Houston Methodist Hospital and Houston Methodist Research Institute, Houston, TX 77030.
authors.forename: Bin
authors.initials: B
authors.lastname: Yuan
authors.affiliation: Baylor Institute for Immunology Research, Baylor Research Institute, Dallas, TX 75204; and yong-jun.liu@baylorhealth.edu zzhang@houstonmethodist.org.
authors.forename: Yong-Jun
authors.initials: YJ
authors.lastname: Liu
authors.affiliation: Baylor Institute for Immunology Research, Baylor Research Institute, Dallas, TX 75204; and Immunobiology and Transplant Research, Houston Methodist Hospital and Houston Methodist Research Institute, Houston, TX 77030 yong-jun.liu@baylorhealth.edu zzhang@houstonmethodist.org.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism*; D003713:Dendritic Cells / Q000201:enzymology / Q000378:metabolism* / Q000821:virology; D053595:Embryonic Stem Cells / Q000201:enzymology / Q000378:metabolism / Q000821:virology; D005347:Fibroblasts / Q000201:enzymology / Q000378:metabolism / Q000821:virology; D051379:Mice; D022423:Myeloid Cells / Q000201:enzymology / Q000378:metabolism* / Q000821:virology; D012328:RNA Viruses / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D012330:RNA, Double-Stranded / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism
chemical_list: D012330:RNA, Double-Stranded; D034741:RNA, Small Interfering; D053487:DEAD-box RNA Helicases