Bovine respiratory disease (BRD) is the leading cause of morbidity and mortality in feedlot cattle with bovine herpesvirus-1 (BHV-1) being the most common source. Currently, research on BHV-1 is hampered by the lack of suitable models for infection and drug testing.
In this study, we established a novel bovine tracheal organoid culture grown in a basement membrane extract type 2 (BME2) matrix and compared it with the air–liquid interface (ALI) culture system. After differentiation, the matrix-embedded organoids developed beating cilia and demonstrated a transcriptomic profile similar to the ALI culture system. The matrix-embedded organoids were highly susceptible to BHV-1 infection and responded to immune stimulation by Pam2Cys, resulting in robust cytokine production and tracheal antimicrobial peptide mRNA upregulation.
Treatment of bovine tracheal organoid cultures with Pam2Cys was not sufficient to inhibit viral infection or replication, suggesting that cell-intrinsic antiviral mechanisms induced by Pam2Cys do not inhibit viral replication when activated in isolation. This implicates a role for the non-epithelial cellular microenvironment in vivo, as the bovine tracheal culture comprises only epithelial cells.
|Treated ALI Organoid