Mapping the journey of a neuro-invasive virus in zebrafish larvae: contrasted viral spread and type I interferon responses in periphery and central nervous system

Sindbis virus (SINV) invades the zebrafish larva CNS from multiple peripheral sites, with 2 to 3 CNS entry events per larva and persistent, variable CNS infection.

• Why it matters: Neuroinvasive spread and the balance between peripheral versus CNS immunity are poorly defined, limiting understanding of how viral encephalitis causes neurological damage.
• What they did: Fluorescent reporter SINV tracked spatial dissemination in transparent zebrafish larvae, while type I interferon control was tested using IFN receptor knockdown and IFN triple mutants plus a quantitative mathematical model.
• The result: Type I IFN responses were systemic in the periphery and local in the CNS, controlling infection in both; modeling estimated 1 to 2 infective virions per productively infected cell per hour and suggested IFN accelerates infected-cell death, with stronger effects in periphery than CNS.

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