From pigs to people: understanding influenza spillover with porcine organoids 2719

Abstract Description Study Objective To understand how influenza strains emerge, evolve, infect and cause disease in animals and humans, better models are needed. Our study objective was to establish a porcine respiratory epithelial organoid model to enable comparative studies in which the regulation of genes in influenza infection could be investigated, and the degree to which they determine productive infection and, therefore, disease. Methods We have established an ex vivo three-dimensional (3D) organotypic air-liquid interface primary porcine respiratory epithelial cell culture system (ALI-PRECs) recreating a cell culture environment morphologically and functionally representative of the epithelial lining of the swine trachea. Using these ALI-PREC models, our laboratory has investigated the molecular pathogenesis of human-, swine-, avian-lineage influenza A virus infection. Results Our studies demonstrated that these viruses trigger an early innate immune response, disrupting mucosal homeostasis and upregulating genes involved in antiviral defense (e.g., STAT2, RSAD2/Viperin, OAS, MX2/MxB, and IFIT4), immune regulation (e.g., PSMB9 and BCL2L14), and cellular processes (e.g., CMAH and MDC1). Conclusions By developing ex vivo culture models that accurately mimic in vivo tissue biology and physiology, we have advanced translational and biomedical research. Our findings lay the groundwork for the development of novel influenza vaccines, diagnostics, and antiviral drugs. Funding Sources Supported by HHS - National Institutes of Health (NIH) CEZID 5P20GM130448 Topic Categories Veterinary and Comparative Immunology (VET)