Pathogen-specific immune responses underlie divergent outcomes of coronavirus and influenza infection in the natural porcine host
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 induced higher viral load and prolonged  viral shedding, stronger systemic and mucosal T cell activation, expansion of memory B cells, and distinct nasal microbiome changes. In contrast pH1N1 resulted in rapid neutralising antibody production, robust Tfh and germinal centre B cell responses, and broader early nasal microbial diversity. Transcriptional responses to PRCV and pH1N1 infection started with the  activation of shared interferon-stimulated genes but later diverged as pathways involvingstromal-immune interactions and vascular integrity shaped lung pathology and subsequent  immune responses. These findings demonstrate 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.
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 induced higher viral load and prolonged  viral shedding, stronger systemic and mucosal T cell activation, expansion of memory B cells, and distinct nasal microbiome changes. In contrast pH1N1 resulted in rapid neutralising antibody production, robust Tfh and germinal centre B cell responses, and broader early nasal microbial diversity. Transcriptional responses to PRCV and pH1N1 infection started with the  activation of shared interferon-stimulated genes but later diverged as pathways involvingstromal-immune interactions and vascular integrity shaped lung pathology and subsequent  immune responses. These findings demonstrate 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.
University of Surrey