Isoferulic acid affords the antiviral potential and restrains white spot syndrome virus proliferation in crayfish (Procambarus clarkii)

Abstract

White spot syndrome virus (WSSV), the causative agent of White spot disease (WSD), not only caused huge economic losses, but also greatly limited the development of crustacean breeding industry. Chinese herbs are widely used and have great application potential in antiviral research. In thist study, the antiviral effects of 11 Chinese herb extracts were evaluated in Procambarus clarkii (crayfish) model of WSSV infection, among which Cimicifuga foetida L. extract showed the highest inhibition rate (88.22%) against WSSV replication. On this basis, the anti-WSSV effect of Isoferulic acid (IFA), a major bioactive component of Cimicifuga foetida L., was further investigated. The results showed that IFA significantly inhibited WSSV replication (96.57%, 50 mg/kg) in a dose-dependent manner and significantly improved the survival of WSSV-challenged crayfish. IFA had the potential preventive and therapeutic effect against WSSV infection, and the preventive effect was better than the therapeutic effect. Mechanistically, IFA suppressed the expression of the immediate early gene ie1, the DNA polymerase gene DNApol and envelope protein gene Vp28 to inhibit WSSV replication, activated TLR, CTL and ProPo genes expression to block ie1 transcription, and suppressed BAF, STAT, NF-κb and Crustin 1 genes expression to elevate innate immunity against WSSV infection. Besides, IFA upregulated the cMnSOD, mMnSOD, CAT and GST genes expression, and downregulated the COX-1 and COX-2 genes expression to balance the oxidative stress and inflammatory damage caused by WSSV infection. This study provides a theoretical basis and meaningful reference for the development of IFA as a highly effective and practical anti-WSSV drug.