A Perspective on Organoids for Virology Research

Animal models and cell lines are invaluable for virology research and host–pathogen interaction studies. However, it is increasingly evident that these models are not sufficient to fully understand human viral diseases. With the advent of three-dimensional organotypic cultures, it is now possible to study viral infections in the human context. This perspective explores the potential of these organotypic cultures, also known as organoids, for virology research, antiviral testing, and shaping the virology landscape.

Because viruses are obligate intracellular parasites, model systems comprising various cellular components are necessary for elucidating their biology. Historically, animal models and immortalized (cancerous) cell lines enabled virology research and host–pathogen interaction studies. Although these model systems immensely contributed to expand our knowledge of virology, the limitations of these models are clear [1]. Animal models do not adequately reproduce human disease pathology, and in some instances, viral pathogens have a unique human tropism that cannot be replicated in a non-natural host. Similarly, cell lines display intrinsic alterations in major signaling pathways, and thus do not recapitulate the homeostatic functions of a normal cell. Cell lines also lack the structural and functional complexity of an organ. These deficiencies often lead to a virus adapting to a cell line after a single passage. This caveat calls for novel validated models that can recapitulate human physiology and are predictive of human disease. Human organoids and organotypic cultures could address this unmet need for human model systems in virology research and antiviral testing. Therefore, in this perspective, we (1) provide an introduction to organoid technology, (2) explore how it could shape the virology landscape, (3) comment on challenges for widespread implementation, and (4) speculate on the future of this technology in the context of viral research.