In vivo evidence for the role of CRFB5 in zebrafish resistance to grass carp reovirus (GCRV) infection.

The interferon (IFN) system is central to vertebrate antiviral innate immunity, whose activation requires the binding of IFNs to specific cell membrane receptors. Teleost IFN receptors CRFB5 is a key component of this receptor complex. However, there is no solid in vivo genetic evidence to verify its physiological function in antiviral defense. Using a zebrafish model, we found that crfb5 expression was rapidly up-regulated in the liver at 4 h post-infection with grass carp reovirus (GCRV). We then constructed crfb5 homozygous knockout zebrafish (crfb5-/-) using CRISPR/Cas9 technology. Challenge with GCRV showed that crfb5-/- zebrafish had a significantly lower survival rate than wild-type (WT) zebrafish. Compared with WT, GCRV-infected crfb5-/- zebrafish showed suppressed mxa expression but elevated levels of ifnφ3 and il6. Collectively, our in vivo data demonstrate that CRFB5 plays a key role in zebrafish anti-GCRV immune response and the maintenance of inflammatory homeostasis by regulating the transcriptional balance of key immune factors.