Brain organoids as versatile models for neurotropic virus research

The resurgence of neurotropic viruses capable of breaching the central nervous system (CNS) has intensified the demand for advanced in vitro models to clarify the mechanisms underlying cellular tropism, neuropathogenesis, and host–virus interactions. Brain organoids (BOs), derived from human pluripotent stem cells, have emerged as physiologically relevant platforms that simulate key features of CNS architecture, cellular diversity, and functional neural circuitry. These three-dimensional systems offer a compelling model for decoding the intricate virus–host interplay within a brain-like microenvironment. This review provides a succinct overview of conventional models employed in neurotropic virus research and summarizes recent innovations in BO technologies. In a novel conceptual pivot, we introduce a functional classification of BO applications based on distinct scientific objectives within neurovirology. Anchoring current findings within this framework provides a more integrative and practical lens through which the evolving utility of BOs can be assessed. Ultimately, we highlight the transformative potential of BOs in accelerating the development of precision therapeutics for CNS infections.