This study investigated how a pre-existing porcine reproductive and respiratory syndrome virus (PRRSV) infection affects subsequent porcine respiratory coronavirus (PRCV) infection in pigs. Researchers infected weaned pigs with PRRSV, then exposed them to PRCV 10 days later. Dual-infected pigs experienced worse outcomes than single-infected animals, including reduced weight gain, higher fever incidence, and more severe pneumonia. The PRRSV infection suppressed innate immune responses, particularly reducing lung interferon-alpha (IFN-α) levels and natural killer cell activity, which correlated with worsened early pneumonia. Later, PRCV infection enhanced PRRSV replication in the lungs and triggered immune responses skewed toward Th1 (IFN-γ) while suppressing Th2 (IL-4) responses, further exacerbating disease. Importantly, PRRSV infection increased alveolar macrophage apoptosis in response to PRCV, suggesting heightened PRRSV replication in these key immune cells. The findings demonstrate interactive effects between the two viruses mediated by both innate and adaptive immune responses, with implications for understanding how immunosuppressive respiratory viral co-infections may worsen disease outcomes in humans and animals.

Key findings

• PRRSV/PRCV dual infection caused more severe pneumonia, fever, and weight loss compared to single viral infections in pigs.
• Pre-existing PRRSV infection suppressed innate immune responses (reduced lung IFN-α and NK cell cytotoxicity), exacerbating early PRCV-induced pneumonia.
• Subsequent PRCV infection enhanced PRRSV replication in lungs and triggered a Th1-skewed immune response (high IFN-γ, low IL-4) that prolonged disease severity.
• PRRSV infection increased pulmonary alveolar macrophage apoptosis during PRCV co-infection, correlating with increased PRRSV replication.