Zebrafish larvae reveal early neuropathology and host responses to nervous necrosis virus

Nervous necrosis virus (NNV) is a major neurotropic pathogen in aquaculture, but early host responses to infection remain poorly defined. Here, we used zebrafish larvae at 4 days post-fertilization and a bath immersion approach to examine the early phase of NNV infection. Infected larvae showed progressive viral accumulation, capsid protein production, and recovery of infectious virus from larval homogenates. Histological and ultrastructural analyses revealed early neural injury, including retinal disruption, mitochondrial swelling, and virus-like particles in brain tissue. Infection was also associated with altered locomotor behavior. Transcriptomic profiling further revealed activation of innate antiviral, oxidative stress, cytokine, and stress-response pathways, together with suppression of genes involved in neuronal maintenance, DNA replication, and cell cycle progression. These findings define an early pathological and transcriptional profile of NNV infection and highlight zebrafish larvae as a useful vertebrate system for studying early host-virus interactions in aquaculture.