Drosophila melanogaster as a translational in vivo platform for modeling Zika virus infection: From experimental approaches to biological discovery.

Zika virus (ZIKV) remains a significant global health concern owing to its association with congenital abnormalities and neurological disease. Although mammalian models have provided important insights into ZIKV biology, complementary systems are needed to enable rapid mechanistic studies and high-throughput genetic analyses. Drosophila melanogaster has emerged as a powerful translational in vivo platform because of its sophisticated genetic toolkit, conserved cellular pathways, and whole-organism experimental accessibility. This review highlights the utility of Drosophila for modeling ZIKV infection, emphasizing experimental approaches used to investigate viral pathogenesis and host responses. We discuss how fly-based studies have advanced understanding of neurodevelopmental defects, tissue tropism, metabolic reprogramming, and innate antiviral immunity while identifying conserved host factors that influence disease outcomes. Finally, we evaluate the strengths and limitations of the model and discuss future applications integrating Drosophila genetics with multi-omics technologies, vertebrate models, and antiviral drug discovery.