What is it about?
A diverse array of fish in Actinopterygii lack the canonical dsRNA pattern recognition receptor retinoic acid-inducible gene I (RIG-I). How do these fish maintain their antiviral immune responses against RNA viruses? We have identified zinc finger NFX1-type containing 1 (ZNFX1) as a novel dsRNA receptor that can compensate for this function. Its antiviral activity against Nervous Necrosis Virus depends on different mechanisms in various cell types.
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Photo by David Clode on Unsplash
Why is it important?
Our findings show that ZNFX1 exhibits stronger antiviral efficacy than MDA5, with heterogeneity across different cell types. In brain cells highly susceptible to NNV and with attenuated regenerative capacity, ZNFX1 suppresses virus-induced interferon responses and pyroptosis, thereby limiting neurotoxicity by precisely tuning the antiviral response. Conversely, in splenic cells with stronger NNV resistance, ZNFX1 directly interacts with TBK1 to trigger a robust interferon response.
Perspectives
Our study highlights ZNFX1 as a compensatory antiviral dsRNA receptor in RIG-I-deficient fish species. It provides mechanistic insights for developing strategies against aquatic NNV and offers novel perspectives for investigating the antiviral innate immune mechanisms in Actinopterygii.
Junfeng Xie
State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University
Read the Original
This page is a summary of: ZNFX1 functions as a compensatory dsRNA recognition receptor to exert antiviral effect in orange-spotted grouper, PLoS Pathogens, October 2025, PLOS,
DOI: 10.1371/journal.ppat.1013652.
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