RT Journal Article T1 Steps of the Replication Cycle of the Viral Haemorrhagic Septicaemia Virus (VHSV) Affecting Its Virulence on Fish A1 López Vázquez, Carmen A1 Bandín Matos, Isabel A1 Panzarin, Valentina A1 Toffan, Anna A1 Cuenca, Argelia A1 Olesen, Niels J. A1 Pereira Dopazo, Carlos K1 Novirhabdovirus K1 Viral cycle K1 Viral production K1 RNA synthesis K1 Trout AB The viral haemorrhagic septicaemia virus (VHSV), a single-stranded negative-sense RNA novirhabdovirus affecting a wide range of marine and freshwater fish species, is a main concern for European rainbow trout (Oncorhynchus mykiss) fish farmers. Its genome is constituted by six genes, codifying five structural and one nonstructural proteins. Many studies have been carried out to determine the participation of each gene in the VHSV virulence, most of them based on genome sequence analysis and/or reverse genetics to construct specific mutants and to evaluate their virulence phenotype. In the present study, we have used a different approach with a similar aim: hypothesizing that a failure in any step of the replication cycle can reduce the virulence in vivo, we studied in depth the in vitro replication of VHSV in different cell lines, using sets of strains from different origins, with high, low and moderate levels of virulence for fish. The results demonstrated that several steps in the viral replication cycle could affect VHSV virulence in fish, including adsorption, RNA synthesis and morphogenesis (including viral release). Notably, differences among strains in any step of the replication cycle were mostly strain-specific and reflected only in part the in vivo phenotype (high and low virulent). Our data, therefore, support the need for further studies aimed to construct completely avirulent VHSV recombinants targeting a combination of genes rather than a single one in order to study the mechanisms of genes interplay and their effect on viral phenotype in vitro and in vivo PB MDPI YR 2020 FD 2020 LK http://hdl.handle.net/10347/24024 UL http://hdl.handle.net/10347/24024 LA eng NO López-Vázquez, C.; Bandín, I.; Panzarin, V.; Toffan, A.; Cuenca, A.; Olesen, N.J.; Dopazo, C.P. Steps of the Replication Cycle of the Viral Haemorrhagic Septicaemia Virus (VHSV) Affecting Its Virulence on Fish. Animals 2020, 10, 2264 NO The project has been funded under the ERANET. The content of this article reflects only the authors’ views, and the ERANET Consortium is not liable for any use that may be made of the information contained therein DS Minerva RD 27 abr 2026