Administration of recombinant IFN1 protects zebrafish (Danio rerio) from ISKNV infection

In the present study, we used the infectious spleen and kidney necrosis virus (ISKNV) and zebrafish model system to investigate the inhibitory effect of recombinant zebrafish interferon 1 (zfrIFN1) on acute viral infection and the impact of time of zfrIFN1 administration on its protective efficacy. In vivo experiments showed that administration of recombinant zfrINF1 up-regulated expression of several IFN-stimulated genes within 24 h of injection, and expression levels of these genes dropped to normal levels similar to those in control fish within three days. However, the transcriptions of two viral genes, the major capsid protein and virus protein 48 genes, were significantly inhibited for at least three days, indicating a longer duration of the zfrIFN1-mediated innate immune effect. To evaluate the protective efficacy of zfrIFN1 against ISKNV infection, we compared the relative percentage survival (RPS) of ISKNV-infected zebrafish by intraperitoneally (IP) injecting the fish with zfrIFN1 at different time points before or after infection. IP injection with 1 μg zfrIFN1/g fish body weight at 24, 6 or 0 h before virus infection or 6 h after virus infection significantly improved fish survival. However, IP injection with an equal dose of zfrIFN1 24 h post-infection did not provide significant protection to the fish. Our results suggest that zfrIFN1 is potent in inhibiting ISKNV acute infection and initiating the innate immune response in zebrafish, but its efficiency depends on the time of administration. This study shows the protective effects of interferon against a DNA-virus in fish for the first time and provides information about the efficacy of fish interferon that will prove useful in possible therapeutic applications.