Influence of Viral Proteins of Avian Influenza Virus on the Innate Immune Response of Birds
We are currently facing a continuing infection cycle caused by a highly pathogenic avian H5N1 influenza virus (hpH5N1) in several countries in Asia. This virus may have the potential to become a pandemic virus. There have been outbreaks of the H5N1 virus in poultry in several countries in Asia since 1997. In 2005 hpH5N1 was first observed outside of Asia in European poultry, which was followed by a fast spread in Europe during February 2006.
The most dangerous property of this hpH5N1 virus is its ability to infect and cause disease in other species than birds including cats, tigers, dogs and stone martens. The INN-FLU consortium integrates nine partners from six EU Member States (Germany, Belgium, United Kingdom, Poland, France and Greece). The project will contribute to an understanding of virus pathogenesis and virulence determinants in chicken, determine host-pathogen interactions and define the molecular basis for host specificity. It is based on four areas of research:
Experiments will address the question of whether HA molecules from non-H5 and non-H7 strains can give low pathogenic viruses the potential to become highly pathogenic. Studies on the host-immune response will focus on the antiviral innate immune response in birds, the role of the influenza virus protein NS1 in contributing to virulence in chickens and expression of genes related to the interferon pathway including Mx.[+] Read More
The continuing outbreaks of disease caused by hpH5N1 in poultry and other birds and of human cases in Asia, Europe and Africa are cause for serious concern. Unlike in the past for hpAIV, there are increased concerns about the potential of this hpH5N1 virus to initiate a human pandemic. It is, however, not possible to predict with certainty if and when this might occur.
The spread of the hpH5N1 virus during the last year was not to be predicted in the observed dimensions, but also emphasised the need for additional knowledge of the disease in poultry, specifically water fowl. In February 2006 the virus entered the European Union with the first description of hpH5N1 in Greece. Whether this occurred via migratory birds is not clear.
It is becoming increasingly evident that hpH5N1 can spread via infected ducks and probably also via other migratory species. The hpH5N1 virus was subsequently isolated from more stationary living birds (e.g. swans) in many EU Member States. This raised great concern with regard to the potential of migratory birds for propagating and spreading these viruses and it underlined the important role of wild birds in viral spread. In addition, these H5N1 viruses become less pathogenic to domestic ducks but remain pathogenic to other domestic poultry.
Host factors which influence the outcome of the hpH5N1 infection and the function of viral elements which influence the virulence of the virus are poorly understood. Research and technological developments will further increase the knowledge of AIV and influenza virus in general. Basic research on virus structure and function, viral pathogenesis, and the host response due to infection will lead to more effective approaches to controlling influenza virus infections.
The principal objectives of the INN-FLU consortium are to use synergies between the partners in order to improve knowledge about the susceptibility of different bird species for AIV, the innate immune response in AIV infected animals and the ecology of AIV, important for the transmission of the infection between wild and domestic birds. The work plan includes exclusively bird species due to the importance of the disease in these species. To achieve this goal an interdisciplinary consortium of experts in molecular virology, genetics, immunology and ornithology has been established. INN-FLU will provide European authorities, policy makers and the community with scientific knowledge enabling a better prediction of potential risks and a successful control of avian influenza.
The scientific aims of the consortium are:
It is expected that the results of the INN-FLU project will contribute significantly to a better understanding of why the new hpH5N1 isolates are able to kill different wild bird species (including water fowl). Infection studies with the hpH5N1 AIV of different species of birds will answer the questions about the induction of disease symptoms as well as the virus excretion in these animals. Also the age dependency for the occurrence of disease symptoms will be explored. This is important since the first line of defence against avian influenza worldwide is surveillance. The results obtained from the infection experiments in combination with the data on bird surveillance during their migration and possible contact points with free range poultry will give a profound basis for an objective, knowledge-based risk assessment. Experiments with the different chicken lines will determine different susceptibility patterns between certain chicken breeds.
Consequently, an increase in the level of genetic resistance provides a possible means of enhancing protection of flocks against AIV infections. The analysis of the innate immune response which is important as the first line of defence against influenza viruses will increase the knowledge about crucial molecular virus-host interactions.
Outbreaks of hpH5N1 in domestic poultry, wild birds and humans have caused serious concerns. The unpredictable speed of the spread of the virus during the last years has left questions about how the virus became present in a number of European countries in a very short time. The INN-FLU project will add useful information for surveillance studies on which birds should be predominantly monitored and which clinical signs can be expected. This will have great impact on monitoring programmes and their design. The knowledge that will be gained in the INN-FLU project with regard to the molecular determinants important for innate immune response and disease pathogenesis will improve and support vaccine developments to control AIV.