Nervous necrosis virus (NNV) causes high mortalities in several marine species. We aimed to evaluate the innate cell-mediated cytotoxic (CMC) activity of head-kidney leucocytes (HKLs) isolated from naïve European sea bass (Dicentrarchus labrax) and gilthead seabream (Sparus aurata), a very susceptible and resistant fish species to NNV, respectively, against fish cell lines infected with NNV. Seabream HKLs showed significantly increased innate CMC activity against NNV-infected cells, compared to those uninfected, while sea bass HKLs failed to do so. Thus, we performed a RNA-seq study to identify genes related to the CMC activity of sea bass leucocytes. Thus, we found that sea bass HKLs incubated with DLB-1 cells alone (CMC_DLB1) or with NNV-infected DLB-1 cells (CMC_DLB1-NNV) showed very similar transcriptomic profiles and the GO analysis revealed that most of the up-regulated genes were related to immunity. Strikingly, when the CMC samples with and without NNV were compared, GO analysis revealed that most of the up-regulated genes in CMC_DLB1-NNV samples were related to metabolism and very few to immunity. This is also in agreement with the functional data. These data point to the escape of CMC activity by NNV infection as an important factor involved in the high susceptibility to nodavirus infections of European sea bass.

This work was supported by grants of the National Bioinformatics Institute (INB), PRB2-ISCIII (PT13/0001/0044 to JG and AE); MINECO (PTA2014‐09515 to MD), MINECO and FEDER (AGL2013-43588-P and AGL2016-74866-C3-1-R to AC) and Fundación Séneca (Grupo de Excelencia de la Región de Murcia 19883/GERM/15). Nodavirus strain and SSN-1 cells were graciously provided by Pilar Fernández Somalo (Laboratorio Central de Veterinaria de Algete, Ministerio de Medio Ambiente, Rural y Marino).