Virus Infection Models: Zebrafish as an Infection Model to Study Immune Landscape During Viral Hemorrhagic Septicemia Virus (VHSV) Infection

ABSTRACT Throughout life, all organisms are subject to viral infections. Smaller sizes and mechanisms that rapidly evolve into new host environments enable viruses to act as major prolific pathogens. Due to the dynamic and complex nature of these interactions between multiple cell types, proteins, and microenvironmental factors, the use of in vivo models may be beneficial for understanding the overall immune landscape rather than being confined to a singular aspect of disease progression. A good example is the difficulty in applying the results observed in in vitro assays to whole animals, revealing a notable discrepancy between studies. In this review, we discuss the feasibility of conducting viral hemorrhagic septicemia virus (VHSV) infection experiments in zebrafish as a laboratory model and different practical approaches to study infection, gene expression patterns, and immune cell dynamics to emphasize the direction of future zebrafish research. Current VHSV outbreaks are primarily managed using vaccines and antiviral drugs; however, their precise mechanisms in fish remain poorly understood. In this review, we address this critical knowledge gap by outlining methods and techniques to study VHSV infection using zebrafish as a model. We discuss how these findings can be applied to other aquaculture species. Additionally, we propose future research directions, particularly at the immune cell level, to deepen our understanding of immune responses during vaccination and antiviral drug treatments to guide the development of more targeted approaches to mitigate pathogen infections.