Immune responses and pathogenesis in immunocompromised chickens in response to infection with the H9N2 low pathogenic avian influenza virus

Abstract

The H9N2 low pathogenic avian influenza (LPAI) viruses have often caused moderate mortality with severe clinical signs in domestic poultry in many Eurasian countries and have occasionally caused clinical respiratory diseases in humans, but the basis for their pathogenesis remains unclear especially in chickens. To better understand the effect of immunosuppression on the risk of H9N2 viral infection, the pathogenesis and host immune responses of the H9N2 LPAI virus in a T-cell-suppressed chicken model were investigated. Cyclosporin A (CsA) treatment led to suppression of cell-mediated immunity such as CD8+ T-cells and reduced expression of IFN-gamma mRNA. T-cell suppression correlated with high viral load in the oropharynx and cloaca of H9N2 LPAI virus-infected specific pathogen free (SPF) chickens. Elevated level of viral RNA in the peripheral blood lymphocytes was found only in immunocompromised chickens. Viral protein and associated cellular apoptosis were observed only in the kidney of the immunocompromised chickens, particularly in those that had died. Our findings suggest that T-cell-mediated responses are important in influenza viral clearance and may help to explain in part the reasons for the increased mortality in chickens infected with H9N2 LPAI viruses in domestic poultry farms.