Project description:Porcine respiratory coronavirus (PRCV) is a naturally occurring pneumotropic coronavirus in the pig, providing a valuable large animal model to study acute respiratory disease. PRCV pathogenesis and the resulting immune response was investigated in pigs, the natural large animal host. We compared two strains, ISU-1 and 135, which induced differing levels of pathology in the respiratory tract to elucidate the mechanisms leading to mild or severe disease. The 135 strain induced greater pathology which was associated with higher viral load and stronger spike-specific antibody and T cell responses. In contrast, the ISU-1 strain triggered mild pathology with a more balanced immune response and greater abundance of T regulatory cells. A higher frequency of putative T follicular helper cells was observed in animals infected with strain 135 at 11 days post-infection. Single-cell RNA-sequencing of bronchoalveolar lavage revealed differential gene expression in B and T cells between animals infected with 135 and ISU-1 at 1 day post infection. These genes were associated with cell adhesion, migration, and immune regulation. Along with increased IL-6 and IL-12 production, these data indicate that heightened inflammatory responses to the 135 strain may contribute to pronounced pneumonia. Among BAL immune cell populations, B cells and plasma cells exhibited the most gene expression divergence between pigs infected with different PRCV strains, highlighting their role in maintaining immune homeostasis in the respiratory tract. These findings indicate the potential of the PRCV model for studying coronavirus induced respiratory disease and identifying mechanisms that determine infection outcomes.
Project description:Coronaviruses and influenza A viruses are major respiratory pathogens with pandemic potential. Using pigs as a translational large-animal model, we compared the virulence, pathogenesis, and immune responses to porcine respiratory coronavirus (PRCV) and pandemic H1N1 2009 influenza virus (pH1N1). PRCV infection resulted in prolonged viral shedding, more severe lung pathology, and higher viral loads in lung tissue and bronchoalveolar lavage fluid, accompanied by pronounced epithelial necrosis and inflammation. Single-cell RNA sequencing at 12 days post-infection revealed distinct transcriptional signatures and immune activation patterns. PRCV induced stronger mucosal and systemic immunity, with elevated IFN-γ, TNF, and IL-2-secreting T cells, and greater numbers of antigen-specific B cells in blood and airways. Nasal microbiome profiling identified both shared and virus-specific alterations. Together, these findings highlight fundamental differences in coronavirus and influenza virus–host interactions and establish the pig as a powerful comparative model for studying respiratory virus pathogenesis and immunity.
Project description:Set of microarray experiments used to identify an unknown coronavirus in a viral culture derived from a patient with SARS. March 2003. Keywords = SARS Keywords = coronavirus Keywords = viral discovery Keywords = viruses Keywords = respiratory infection
