Immunogenetics of antiviral immunity in ducks

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My NSERC research program is focused on the immunogenetics of the wild duck population and its influence on their role as host of influenza. We know that 15-30% of wild ducks are infected with influenza in Canadian lakes at any time. We would like to know how ducks clear the virus, and be able to correlate the genetics of ducks with their disease susceptibility/resistance. This would be useful to know for farming resistant ducks, as well as conservation efforts aimed at maintaining a healthy population of wild ducks in the ecosystem, and for hunting. Three arms of the immune response are involved in clearing viruses; antibodies, adaptive immunity involving white blood cells that kill infected cells, and innate immunity. We believe that impaired adaptive immunity is responsible for their exploitation as the host of most strains of influenza, while innate immunity allows them to survive highly pathogenic avian influenza. Our long-term goal is to understand these host-pathogen interactions from an immunology perspective, and understand the role of genetic diversity in host immune responses. The genes that control the host immune response are located on one chromosome in the Major Histocompatibility Complex. The diversity of these genes in the species determines their success against viral pathogens. We are exploring the diversity of genes that control three kinds of white blood cells, the helper and cytotoxic T cells and the Natural Killer cells. We have blood samples from 50 wild mallard ducks and we have used these to examine diversity of the genes for MHC class I that allow presentation of viral peptides to cytotoxic T cells. Our data show that ducks have a lot of diversity in the population, but individuals use only one gene while humans use 3 genes. The proteins made by this one gene can present a much smaller number of viral proteins to enable detection. This is likely to limit the ability of ducks to see influenza infected cells, and contributes to why ducks are the host of influenza. One puzzle we are trying to understand is that the expression of these genes is too early for adaptive immunity. We know these proteins (in humans) are involved also in NK cell recognition and perhaps this is why they are expressed so early. NK cells are first responders to a viral infection. To know how NK cells in ducks work, we will identify NK cell receptors from our 50 ducks. Again we expect these to be different between individuals, and some may be better at controlling NK cell killing. Our research will contribute to understanding the ways in which influenza viruses exploit the duck as a host and reservoir. While we focus mainly on wild ducks, this work can inform breeding and selection of influenza-resistant ducks and conservation of natural populations in the wild.