Virus transmission dynamics and the immune response of birds to avian influenza.

The global spread of H5N1 highly pathogenic avian influenza viruses and their ability to infect not only birds but humans emphasises that human and animal health are unavoidably linked. At present avian influenza remains an animal disease problem under urgent need for control but control in birds will also reduce the potential for a human influenza pandemic. Our knowledge of the behaviour of avian influenza viruses in domestic fowl and wild birds is limited. This proposal poses some fundamental questions that address how the easily the virus can infect chickens, turkeys and ducks; how much, and for how long, virus is shed following infection in each species; and how avian influenza virus infection is controlled by the immune response of birds. Fundamental studies of this type will be critical to the design and implementation of control measures in the short term and the long term.

At present H5N1 avian influenza is an animal disease problem under urgent need of control. The widespread occurrence and wide host range of the H5N1 virus poses a serious threat to the human population, potentially leading to the evolution of a human influenza pandemic. Our knowledge of the behaviour of avian influenza viruses in domestic fowl and wild birds is limited. Virus infection dynamics of H7N1 low and high pathogenicity avian influenza viruses and highly pathogenic H5N1 viruses in chickens, turkeys and ducks will be compared. Extensive in-depth sequence analysis of the virus haemagglutinin gene will be undertaken to examine within-host selection of virus variants in each species- avian host range determinants. We also will determine whether in-bred chickens lines show genetic differences in susceptibility to infection and in virus shedding, and whether there are genetic differences in the immune response of the in-bred lines to infection and vaccination- these studies can provide a starting point to uncovering the genetic basis of host resistance to influenza virus infection. The immune response to infection will be studied at tissue level, and protective cellular, humoral and cytokine responses will be defined.