New insights into how the immune system responds to influenza and coronavirus infections have been revealed in a study led by researchers at The Pirbright Institute. The findings could inform future vaccines and treatments for respiratory diseases in humans.
Scientists used pigs, whose respiratory systems closely resemble those of humans, to investigate how two major respiratory viruses, pandemic H1N1 influenza (pH1N1) and porcine respiratory coronavirus (PRCV) affect viral replication, lung damage, immune responses and airway microbiota.
The comprehensive international study, published in Nature Communications Biology, found PRCV infection resulted in higher viral loads, prolonged viral shedding, and more severe lung pathology compared to pH1N1. While influenza virus levels declined more rapidly, PRCV persisted longer in the respiratory tract, causing broader tissue damage.
Professor Elma Tchilian, Head of Mucosal Immunology at Pirbright, said: “The work revealed some interesting findings. Influenza-infected lungs showed greater early infiltration of immune cells, including T cells and macrophages, which may contribute to faster viral clearance and reduced tissue damage. In contrast, PRCV infection caused more widespread injury with less localized immune cell recruitment in early stages.”
Both viruses triggered antibody responses, but their timing and characteristics differed significantly. Influenza infection induced faster and stronger neutralising antibody responses, supported by increased activity of T follicular helper cells and plasma cells.
PRCV, however, stimulated a more pronounced expansion of memory B cells, suggesting a longer-term immune imprint but delayed neutralising activity, which may explain the prolonged viral persistence observed in PRCV infections.
“Responses from specialised protective T cells also varied,” added co-author and PhD student Ehsan Sedaghat-Rostami. “PRCV infection led to stronger and more widespread activation of T-cells producing cytokines – the small signalling proteins that act as chemical messengers to regulate immunity. Influenza responses were more localized to the respiratory tract and less pronounced systemically.”
Additionally, PRCV triggered an increase in regulatory T cells, indicating activation of mechanisms help control inflammation and promote recovery.
At the molecular level, both viruses initially activated similar antiviral pathways, particularly interferon-stimulated genes, across multiple cell types. However, by later stages of infection, their effects diverged.
The research project brought together expertise from the United Kingdom Health Security Agency, the University of Surrey and Babraham Institute in the UK, Utrecht University in the Netherlands and Ghent University in Belgium.
Its results show both viruses altered the nasal microbiome in distinct ways. Both increased levels of Streptococcaceae, a group which includes opportunistic pathogens. However, PRCV was associated with enrichment of Micrococcaceae, while influenza infection led to greater overall microbial diversity and reductions in bacteria linked to respiratory health.
These findings suggest virus-specific changes in airway bacteria could influence disease severity and susceptibility to secondary infections.
“Our study highlights the importance of tailoring vaccines and therapies to the specific immune signatures of different viruses,” added Professor Tchilian. “Understanding these differences is critical for improving prevention and treatment strategies for respiratory infections.”
The study shows influenza and coronaviruses share some early immune activation pathways, but they diverge significantly in their interaction with the host over time, affecting viral persistence, immune memory, inflammation, and even the airway microbiome.
Read the paper: Pathogen-specific immune responses might underlie divergent outcomes of coronavirus and influenza infection in the natural porcine host
DOI: 10.1038/s42003-026-10400-y