|ZFIN ID: ZDB-PUB-150515-5|
Conservation of the STING-mediated cytosolic DNA sensing pathway in zebrafish
Ge, R., Zhou, Y., Peng, R., Wang, R., Li, M., Zhang, Y., Zheng, C., Wang, C.
|Source:||Journal of virology 89(15): 7696-706 (Journal)|
|PubMed:||25972544 Full text @ J. Virol.|
Ge, R., Zhou, Y., Peng, R., Wang, R., Li, M., Zhang, Y., Zheng, C., Wang, C. (2015) Conservation of the STING-mediated cytosolic DNA sensing pathway in zebrafish. Journal of virology. 89(15):7696-706.
ABSTRACTZebrafish (Danio rerio) is a unique and potential model animal for dissecting innate immune signalings. Here, we demonstrate that herpes simplex virus type -1(HSV-1) could infect zebrafish at its different developmental stages, and trigger the expression of type I interferons (IFNs) as well as ISGs in zebrafish larva. 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 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.
Importance The zebrafish larva provides technical advantages for understanding host-pathogen interactions. In this study, we establish 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.