title: Conservation of the STING-Mediated Cytosolic DNA Sensing Pathway in Zebrafish.
abstract: Zebrafish (Danio rerio) is a unique potential model animal for dissecting innate immune signaling. Here we demonstrate that herpes simplex virus 1 (HSV-1) could infect zebrafish at its different developmental stages and trigger the expression of type I interferons (IFNs) as well as interferon-stimulated genes (ISGs) in zebrafish larvae. Silencing of zSTING, but not zMAVS, markedly attenuates the DNA virus-induced antiviral responses. Notably, a conserved serine residue (S373) is essential for the action of zSTING. Unexpectedly, zebrafish cyclic GMP-AMP synthase (cGAS) is dispensable for the STING signaling, whereas zDHX9 and zDDX41 are potential sensors for HSV-1 infection in vivo. Taken together, this proof-of-concept study establishes the zebrafish larva as a feasible model for investigating the cytosolic DNA sensing mechanism, shedding light on the conservation of the STING antiviral signaling pathway.
  
  
  OBJECTIVE
  The zebrafish larva provides technical advantages for understanding host-pathogen interactions. In this study, we established the zebrafish larva as a useful model for studying HSV-1 infection. HSV-1 infection triggers strong type I interferon production, which depends on STING expression. In addition, STING-mediated antiviral signaling is conserved in zebrafish. Interestingly, zDHX9 and zDDX41 are indispensable for detecting HSV-1, while cGAS is dispensable. This proof-of-concept study indicates that the zebrafish represents an amenable model for the investigation of cytosolic DNA sensing mechanisms.
authors.affiliation: State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Ge
authors.affiliation: State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Peng
authors.affiliation: State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Mi
authors.initials: M
authors.lastname: Li
authors.affiliation: State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Yunbin
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Institutes of Biology and Medical Sciences, Soochow University, Suzhou, China.
authors.forename: Chunfu
authors.initials: C
authors.lastname: Zheng
authors.affiliation: State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China cwang01@sibcb.ac.cn.
authors.forename: Chen
authors.initials: C
authors.lastname: Wang
mesh_terms: D000818:Animals; D003600:Cytosol / Q000276:immunology / Q000821:virology*; D004279:DNA, Viral / Q000235:genetics / Q000276:immunology*; D004195:Disease Models, Animal; D006561:Herpes Simplex / Q000235:genetics / Q000276:immunology* / Q000821:virology; D018259:Herpesvirus 1, Human / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D006801:Humans; D007370:Interferon Type I / Q000235:genetics / Q000276:immunology; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology*; D015027:Zebrafish / Q000235:genetics / Q000276:immunology* / Q000821:virology; D029961:Zebrafish Proteins / Q000235:genetics / Q000276:immunology*; D000099197:STING Protein
chemical_list: D004279:DNA, Viral; D007370:Interferon Type I; D008565:Membrane Proteins; D029961:Zebrafish Proteins; C000601909:sting1 protein, zebrafish; D000099197:STING Protein