RT Journal Article T1 Cytokine-like activity of European sea bass ISG15 protein on RGNNV-infected E−11 cells A1 Moreno-García, Patricia A1 Leiva-Rebollo, Rocío A1 García-Rosado, Esther A1 Béjar-Alvarado, Julia A1 Alonso-Sánchez, María del Carmen K1 Lubinas AB IFN-I generates an antiviral state by inducing the expression of numerous genes, called IFN-stimulated genes,ISGs, including ISG15, which is the only ISG with cytokine-like activity. In a previous study, we developed theDl_ISG15_E11 cell line, which consisted of E11 cells able to express and secrete sea bass ISG15. The current studyis a step forward, analysing the effect of secreted sea bass ISG15 on RGNNV replication in E11 cells, and lookinginto its immunomodulatory activity in order to corroborate its cytokine-like activity. The medium from ISG15-produccing cells compromised RGNNV replication, as it has been demonstrated both, by reduction in the viralgenome synthesis and, specially, in the yield of infective viral particles. The implication of sea bass ISG15 in thisprotection has been demonstrated by ISG15 removal, which decreased the percentage of surviving cells uponviral infection, and by incubation of RGNNV-infected cells with a recombinant sea bass ISG15 protein, whichresulted in almost full protection. Furthermore, the immunomodulatory activity of extracellular sea bass ISG15has been demonstrated, which reaffirms a cytokine-like role for this protein PB Elsevier YR 2022 FD 2022-08-23 LK https://hdl.handle.net/10630/24929 UL https://hdl.handle.net/10630/24929 LA eng NO This study has been supported by projects AGL2017-84644-R (MINECO/AEI/FEDER, UE) (Spanish Government) and UMA20-FEDERJA-103 (Consejería de Economía y Conocimiento/Programa Operativo FEDER 2014–20, UE) (Junta de Andalucía). Funding for open access charge: Universidad de Málaga/CBUA. Authors thank I. Bandin for the viral isolate. NO This study has been supported by projects AGL2017-84644-R (MINECO/AEI/FEDER, UE) (Spanish Government) and UMA20-FEDERJA-103 (Consejería de Economía y Conocimiento/Programa Operativo FEDER 2014–20, UE) (Junta de Andalucía). Funding for open access charge: Universidad de M ́alaga/CBUA. Authors thank I. Bandin for the viral isolate. DS RIUMA. Repositorio Institucional de la Universidad de Málaga RD 20 ene 2026