title: The interaction between the helicase DHX33 and IPS-1 as a novel pathway to sense double-stranded RNA and RNA viruses in myeloid dendritic cells.
abstract: In eukaryotes, there are at least 60 members of the DExD/H helicase family, many of which are able to sense viral nucleic acids. By screening all known family members, we identified the helicase DHX33 as a novel double-stranded RNA (dsRNA) sensor in myeloid dendritic cells (mDCs). The knockdown of DHX33 using small heteroduplex RNA (shRNA) blocked the ability of mDCs to produce type I interferon (IFN) in response to poly I:C and reovirus. The HELICc domain of DHX33 was shown to bind poly I:C. The interaction between DHX33 and IPS-1 is mediated by the HELICc region of DHX33 and the C-terminal domain of IPS-1 (also referred to MAVS and VISA). The inhibition of DHX33 expression by RNA interference blocked the poly I:C-induced activation of MAP kinases, NF-κB and IRF3. The interaction between the helicase DHX33 and IPS-1 was independent of RIG-I/MDA5 and may be a novel pathway for sensing poly I:C and RNA viruses in mDCs.
authors.affiliation: Department of Infectious Diseases, The First Hospital, Jilin University, Changchun, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Immunology, Center for Cancer Immunology Research, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Ning
authors.initials: N
authors.lastname: Lu
authors.affiliation: Department of Immunology, Center for Cancer Immunology Research, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Bin
authors.initials: B
authors.lastname: Yuan
authors.affiliation: Baylor Institute for Immunology Research, Baylor Research Institute, Dallas, TX, USA.
authors.forename: Leiyun
authors.initials: L
authors.lastname: Weng
authors.affiliation: Department of Infectious Diseases, The First Hospital, Jilin University, Changchun, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.affiliation: Baylor Institute for Immunology Research, Baylor Research Institute, Dallas, TX, USA.
authors.forename: Yong-Jun
authors.initials: YJ
authors.lastname: Liu
authors.affiliation: Baylor Institute for Immunology Research, Baylor Research Institute, Dallas, TX, USA.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D053487:DEAD-box RNA Helicases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D047468:Immunoprecipitation; D051379:Mice; D022423:Myeloid Cells / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D011070:Poly I-C / Q000378:metabolism; D012328:RNA Viruses / Q000276:immunology* / Q000378:metabolism; D012330:RNA, Double-Stranded / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D016207:Cytokines; D053487:DEAD-box RNA Helicases; D016328:NF-kappa B; D011070:Poly I-C; D012330:RNA, Double-Stranded; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C512612:MAVS protein, mouse; C581514:DHX33 protein, mouse
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