title: LSm14A Plays a Critical Role in Antiviral Immune Responses by Regulating MITA Level in a Cell-Specific Manner.
abstract: Viral infection triggers induction of antiviral cytokines and effectors, which are critical mediators of innate antiviral immune response. It has been shown that the processing body-associated protein LSm14A is involved in the induction of antiviral cytokines in cell lines but in vivo evidence is lacking. By generating LSm14A-deficient mice, in this study, we show that LSm14A plays a critical and specific role in the induction of antiviral cytokines in dendritic cells (DCs) but not in macrophages and fibroblasts. Induction of antiviral cytokines triggered by the DNA viruses HSV-1 and murid herpesvirus 68 and the RNA virus vesicular stomatitis virus but not Sendai virus was impaired in Lsm14a(-/-) DCs, which is correlated to the functions of the adaptor protein MITA/STING in the antiviral signaling pathways. LSm14A deficiency specifically downregulated MITA/STING level in DCs by impairing its nuclear mRNA precursor processing and subsequently impaired antiviral innate and adaptive immune responses. Our findings reveal a nuclear mRNA precursor processing and cell-specific regulatory mechanism of antiviral immune responses.
authors.affiliation: College of Life Sciences, Medical Research Institute, Collaborative Innovation Center for Viral Immunology, State Key Laboratory of Virology, Wuhan University, Wuhan 430072, China; and.
authors.forename: Tian-Tian
authors.initials: TT
authors.lastname: Liu
authors.affiliation: College of Life Sciences, Medical Research Institute, Collaborative Innovation Center for Viral Immunology, State Key Laboratory of Virology, Wuhan University, Wuhan 430072, China; and.
authors.forename: Qing
authors.initials: Q
authors.lastname: Yang
authors.affiliation: College of Life Sciences, Medical Research Institute, Collaborative Innovation Center for Viral Immunology, State Key Laboratory of Virology, Wuhan University, Wuhan 430072, China; and.
authors.forename: Mi
authors.initials: M
authors.lastname: Li
authors.affiliation: College of Life Sciences, Medical Research Institute, Collaborative Innovation Center for Viral Immunology, State Key Laboratory of Virology, Wuhan University, Wuhan 430072, China; and.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhong
authors.affiliation: Wuhan Institute of Virology, State Key Laboratory of Virology, Chinese Academy of Sciences, Wuhan 430071, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Ran
authors.affiliation: Wuhan Institute of Virology, State Key Laboratory of Virology, Chinese Academy of Sciences, Wuhan 430071, China.
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Liu
authors.affiliation: Wuhan Institute of Virology, State Key Laboratory of Virology, Chinese Academy of Sciences, Wuhan 430071, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Wuhan Institute of Virology, State Key Laboratory of Virology, Chinese Academy of Sciences, Wuhan 430071, China.
authors.forename: Yan-Yi
authors.initials: YY
authors.lastname: Wang
authors.affiliation: College of Life Sciences, Medical Research Institute, Collaborative Innovation Center for Viral Immunology, State Key Laboratory of Virology, Wuhan University, Wuhan 430072, China; and shuh@whu.edu.cn.
authors.forename: Hong-Bing
authors.initials: HB
authors.lastname: Shu
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology / Q000821:virology; D005347:Fibroblasts / Q000276:immunology / Q000821:virology; D006564:Herpesviridae / Q000276:immunology; D018259:Herpesvirus 1, Human / Q000276:immunology; D054884:Host-Pathogen Interactions; D007113:Immunity, Innate; D008264:Macrophages / Q000276:immunology / Q000821:virology; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D011506:Proteins / Q000235:genetics / Q000502:physiology*; D029082:Sendai virus / Q000276:immunology; D015398:Signal Transduction; D014721:Vesicular stomatitis Indiana virus / Q000276:immunology; D000099197:STING Protein
chemical_list: D016207:Cytokines; D008565:Membrane Proteins; D011506:Proteins; C549049:LSM14A protein, mouse; C530855:Sting1 protein, mouse; D000099197:STING Protein