The Role of Human Intestinal Enteroids as a Platform to Assess Norovirus Prevention and Control Interventions

Verónica Costantini, Centers for Disease Control and Prevention

Jan Vinjé, Division of Viral Diseases, Centers for Disease Control and Prevention, Atlanta, GA

Prevention & Control (antivirals)

Research on human infectious diseases has historically been limited by the absence of robust in vitro models that accurately recapitulate human physiology and disease. This limitation was especially pronounced for human norovirus, as the inability to culture the virus in traditional cell lines posed a significant barrier to progress in virology, epidemiology, and public health. The development of the human intestinal enteroid (HIE) model—multicellular, physiologically relevant cultures derived from tissue-specific stem cells—has fundamentally transformed norovirus research. HIEs closely mimic the architecture and function of the human intestinal epithelium, enabling norovirus replication and supporting studies of viral pathogenesis, host interactions, and strain diversity. Here, we review and summarize progress achieved at CDC and through collaborations with other research groups using the HIE model. The impact of the HIE model spans multiple domains of public health: they have empowered researchers to address essential questions about norovirus transmission, environmental stability, and host susceptibility. Surveillance programs now leverage HIEs to assess strain-specific infectivity and pathogenicity, while studies on disease prevention and control benefit from the ability to evaluate antiviral agents, vaccine candidates and non-pharmaceutical interventions in a human-relevant system. HIEs have also advanced environmental and food safety research by enabling the assessment of decontamination strategies and risk of infection from diverse sources. While challenges remain and further refinements are needed, the HIE model has catalyzed significant advances in understanding norovirus biology and continues to support public health initiatives aimed at reducing the global burden of norovirus disease.