Human gut organoids A promising model to study virus infection and pathogenesis processes

This thesis focuses on the need for a human physiological culture system to study viral infections. It highlights the limitations of using cell lines and animal models for understanding human virus-host interactions in the gut. The thesis specifically explores the dynamics of virus-host interactions involving enterovirus A71 (EV-A71) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in human gut organoids.
Chapter 1 introduces the need for a human model for studying viral infections. Chapter 2 reviews data translation from animal models to human viral diseases, spotlighting the challenges of interpretation and the need for standardization. Chapter 3 presents a method for creating a standardized primary cell monolayer model of the human fetal intestinal epithelium using human intestinal organoids. This model is characterized for various aspects and used to study infectious diseases. Chapter 4 applies the human intestinal epithelial model to evaluate EV-A71 pathogenesis. The study identifies the importance of a specific amino acid, glutamine at position 145 of the viral capsid protein VP1, for EV-A71 infection in the human intestine. The chapter also discusses the potential implications of this finding for viral spread and secondary infections. Chapter 5 explores the protective ability of human milk against SARS-CoV-2 infection using the same model. It finds that human milk inhibits SARS-CoV-2 replication, regardless of the presence of specific antibodies. The chapter also suggests that the inhibition may be related to the down-regulation of ATPase Na+/K+ Transporting Subunit Alpha 1 (ATP1A1). In conclusion, the work underlines the value of the human intestinal epithelial model in viral research, suggesting its potential for both basic research and clinical applications while aiming to minimize animal model use.