Viral interference between infectious pancreatic necrosis virus and spring viremia of carp virus in zebrafish

Fish birnaviruses and rhabdoviruses are major causes of diseases that pose a threat to the fish farming industry. In this work we investigated the interaction between IPNV (birnavirus) and SVCV (rhabdovirus) in a zebrafish model where SVCV is lethal while IPNV causes asymptomatic infection. Two situations were analyzed: 1) A primary IPNV infection followed by a second challenge with SVCV; 2) SVCV as the first infection and a second challenge with IPNV. Irrespective of the order of infections, IPNV increased survival of SVCV-infected fish, reflecting viral interference that correlated with the inhibition of SVCV RNA synthesis. In contrast, in some instances a synergistic effect occurred between SVCV and IPNV: IPNV replication was enhanced in mixed infections with SVCV compared to the single IPNV infection. Expression of host immune response genes il1b, mx and gig2 was modulated differently depending on the order of virus infections: while higher levels of expression of il1b, mx and gig2 were found in fish infected first with IPNV, those three genes were down-regulated in fish infected with SVCV and then challenged with IPNV. This first report of mixed birnavirus/rhabdovirus infections in zebrafish may help to identify those factors associated to disease resistance and cross-protection in fish, with practical implications for the development of new strategies for virus control in aquaculture.