Deciphering European Sea Bass (Dicentrarchus labrax) Resistance to Nervous Necrosis Virus by Transcriptome Analysis from Early Infection Towards Establishment of Virus Carrier State

Viral nervous necrosis, caused by the nervous necrosis virus (NNV), is an important threat to aquaculture, causing great economic losses and a high environmental burden. European sea bass (<i>Dicentrarchus labrax</i>) is highly affected by NNV, and selective breeding programs for disease resistance have been established in order to achieve a sustainable aquaculture and minimize the need for vaccines, drugs and antibiotics. Resistant and susceptible European sea bass were experimentally challenged with NNV and their head kidney transcriptomes were analyzed at three time points, i.e., 3 hpi, 2 dpi and 14 dpi. Numerous differentially expressed genes (DEGs) were identified in the head kidneys of resistant and susceptible infected vs. non-infected sea bass. Gene ontology enrichment, pathway, and protein-protein interaction analyses revealed that the NNV-resistant fish control their response to viral infection more efficiently, utilizing different mechanisms compared to the susceptible fish. Resistant fish displayed higher levels of interferon-related elements, cytokines, antigen presentation, T-cell activity, apoptosis, and programmed cell death combined with a controlled inflammatory response and more active proteasome and lysosome functions. The susceptible fish appeared to have high immune responses at the early infection stages, accompanied by high expressions of inflammatory, complement and coagulation pathways. Insulin metabolism was better regulated in the resistant fish and the control of lipid metabolism was less effective in the susceptible family. The cytoskeleton- and cell adhesion-related pathways were mostly down-regulated in the susceptible fish, and the intracellular transport and motor proteins were utilized more efficiently by the resistant fish. The present study represents a thorough transcriptomic analysis of NNV infection effects on a resistant and a susceptible European sea bass head kidney. The obtained results provide valuable information on the mechanisms that offers pathogen resistance to a host, with many aspects that can be exploited to develop more efficient approaches to fighting viral diseases in aquaculture.