Oxysterols are a family of cholesterol oxygenated derivatives with diverse roles in many biological activities and have recently been linked with the induction of a cellular antiviral state. The antiviral effects of 25-hydroxycholesterol (25HC) extend to several mammalian enveloped and non-enveloped viruses. It has been reported that the expression of the gene encoding cholesterol 25-hydroxylase (CH25H) is induced by interferons (IFNs). In this work, five ch25h genes were identified in the zebrafish (Danio rerio) genome. The ch25h genes showed different tissue expression patterns and differed in their expression after immune stimulation with lipopolysaccharide (LPS), polyinosinic:polycytidylic acid (PolyI:C) and Spring Viremia Carp Virus (SVCV). Only one of the 5 genes, ch25hb, was overexpressed after the administration of the treatments. Synteny and phylogenetic analyses revealed that ch25hb is the putative homolog of mammalian Ch25h in zebrafish, while the remaining zebrafish ch25h genes are products of duplications within the teleost lineage. Interestingly, its modulation was not mediated by type I IFNs, contrasting previous reports on mammalian orthologs. Nevertheless, in vivo overexpression of ch25hb in zebrafish larvae significantly reduced mortality after SVCV challenge. Viral replication was also negatively affected by 25HC administration to the zebrafish cell line ZF4. In conclusion, the interferon-independent antiviral role of 25HC was extended to a non-mammalian species for the first time, and dual activity that both protects the cells and interacts with the virus cannot be discarded.

氧固醇是胆固醇氧化衍生物的家族，在许多生物学活动中具有多种作用，并且最近与诱导细胞抗病毒状态有关。25-羟基胆固醇（25HC）的抗病毒作用扩展到了几种哺乳动物的包膜和非包膜病毒。据报道，干扰素（IFN）诱导了编码胆固醇25-羟化酶（CH25H）的基因的表达。在这项工作中，在斑马鱼（Danio rerio）基因组中鉴定出五个ch25h基因。该ch25h在用脂多糖（LPS），多肌苷酸：聚胞苷酸（PolyI：C）和春季病毒性鲤鱼病毒（SVCV）免疫刺激后，这些基因显示出不同的组织表达模式，并且其表达也有所不同。在给予这些治疗后，这5个基因中只有ch25hb基因之一过表达。同源性和系统发育分析表明，ch25hb是斑马鱼中哺乳动物Ch25h的推定同源物，而其余​​的斑马鱼ch25h基因是硬骨鱼类谱系中重复的产物。有趣的是，它的调节不是由I型IFN介导的，这与以前有关哺乳动物直系同源物的报道形成了对比。尽管如此，体内ch25hb的过度表达在斑马鱼的幼虫中，SVCV攻击后死亡率显着降低。病毒复制也受到25HC给予斑马鱼细胞系ZF4的负面影响。总之，25HC的不依赖干扰素的抗病毒作用首次扩展到非哺乳动物物种，不能同时保护细胞和与病毒相互作用的双重活性。