Hepcidin peptide controls the inflammatory response induced by betanodavirus infection and improves European sea bass (Dicentrachus labrax) survival

Nervous necrosis virus (NNV) is the etiological agent of viral encephalopathy and retinopathy in many fish species, including European sea bass (Dicentrachus labrax) and is of great economic losses to fish farmers. To solve this problem in fish production, antimicrobial peptides (AMPs) have been identified as potential candidates for NNV treatment in aquaculture. Hepcidin (Hamp) is one of the most promising AMPs. Thus, we aimed to evaluate the therapeutic application of Hamp synthetic peptide after NNV challenge. Hamp was able to significantly increase survival rates and ameliorate clinical signs of the disease, though the viral levels, determined by viral replication and immunolocalization, were not affected. Synthetic Hamp increased the immunoglobulin M (IgM) and AMP protein levels in serum and some tissues respect to the levels found in NNV-infected fish. However, Hamp peptide decreased the NNV-induced bactericidal activity. At the gene level, Hamp exerted anti-inflammatory properties, reducing the pro-inflammatory response orchestrated by NNV, probably preventing neuronal damage. Apart from this, Hamp up-regulated the expression of adhesion molecules that facilitated the recruitment of immune cells, namely T helper and B cells, probably to orchestrate the adaptive response. To conclude, Hamp immunomodulatory properties and therapeutic application against NNV are very promising for its use in aquaculture.