title: TRIM56 is an essential component of the TLR3 antiviral signaling pathway.
abstract: Members of the tripartite motif (TRIM) proteins are being recognized as important regulators of host innate immunity. However, specific TRIMs that contribute to TLR3-mediated antiviral defense have not been identified. We show here that TRIM56 is a positive regulator of TLR3 signaling. Overexpression of TRIM56 substantially potentiated extracellular dsRNA-induced expression of interferon (IFN)-β and interferon-stimulated genes (ISGs), while knockdown of TRIM56 greatly impaired activation of IRF3, induction of IFN-β and ISGs, and establishment of an antiviral state by TLR3 ligand and severely compromised TLR3-mediated chemokine induction following infection by hepatitis C virus. The ability to promote TLR3 signaling was independent of the E3 ubiquitin ligase activity of TRIM56. Rather, it correlated with a physical interaction between TRIM56 and TRIF. Deletion of the C-terminal portion of TRIM56 abrogated the TRIM56-TRIF interaction as well as the augmentation of TLR3-mediated IFN response. Together, our data demonstrate TRIM56 is an essential component of the TLR3 antiviral signaling pathway and reveal a novel role for TRIM56 in innate antiviral immunity.
authors.affiliation: Department of Microbiology, Immunology, and Biochemistry, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA.
authors.forename: Yang
authors.initials: Y
authors.lastname: Shen
authors.forename: Nan L
authors.initials: NL
authors.lastname: Li
authors.forename: Jie
authors.initials: J
authors.lastname: Wang
authors.forename: Baoming
authors.initials: B
authors.lastname: Liu
authors.forename: Sandra
authors.initials: S
authors.lastname: Lester
authors.forename: Kui
authors.initials: K
authors.lastname: Li
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D000595:Amino Acid Sequence; D057809:HEK293 Cells; D006367:HeLa Cells; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006526:Hepatitis C / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D050838:Interferon Regulatory Factor-3 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D016899:Interferon-beta / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D017384:Sequence Deletion; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D051196:Toll-Like Receptor 3 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; C494232:IRF3 protein, human; D050838:Interferon Regulatory Factor-3; C470409:TICAM1 protein, human; C495344:TLR3 protein, human; D051196:Toll-Like Receptor 3; D000070584:Tripartite Motif Proteins; D016899:Interferon-beta; C554560:TRIM56 protein, human; D044767:Ubiquitin-Protein Ligases