Pathogen-specific immune responses might underlie divergent outcomes of coronavirus and influenza infection in the natural porcine host

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.