Innate Antiviral Defenses In The Natural Host Of Influenza, The Duck

Ducks and wild waterfowl perpetuate most strains of influenza A viruses in nature. In their natural host, influenza viruses typically cause asymptomatic infection and little pathology. Ducks are often unharmed by influenza viruses capable of killing chickens. We are investigating the reasons underlying the difference in susceptibility of these birds, with the aim of identifying the effectors of a successful immune response to influenza. We show that the influenza virus sensor, RIG-I, is present in ducks and absent in chickens, providing a partial explanation for the increased susceptibility to influenza viruses of chickens compared with ducks. RIG-I detects uncapped viral RNA transcripts and initiates the interferon response. We show that the chicken embryonic fibroblast cell line, DF-1, cannot respond to a RIG-I ligand. However, transfection of duck RIG-I into DF-1 cells rescues the detection of ligand and induces interferon-beta promoter activity. Additionally, DF-1 cells expressing duck RIG-I have an augmented interferon response resulting in decreased influenza replication after challenge with either low or highly pathogenic avian influenza virus. Using chicken microarrays we show that key innate immune genes are upregulated by influenza infection in the presence of duck RIG-I compared to cells carrying vector only. Implicating RIG-I in the antiviral response to a natural infection in ducks, we found that RIG-I expression is induced 200 fold, early in an innate immune response in ducks challenged with A/Vietnam/1203/04 (H5N1). In contrast, infection with the duck isolate A/British Columbia 500/2005 (H5N2) only slightly increases expression of RIG-I in lung or intestine. Interferon-stimulated genes downstream of RIG-I signaling are upregulated >1000-fold in VN1203 infected duck lung, but much less in the BC500 infected intestine. The different response may be due to tissue tropism of the strains and immune capability of these tissues, or viral subversion of the response. Ultimately, the duck immune response confers protection against highly pathogenic strains while permitting propagation of low pathogenic strains.