Avian influenza could be stopped in its tracks by a new technique from researchers at the UK universities of Cambridge and Edinburgh. The scientists have successfully developed genetically modified (transgenic) chickens that cannot transmit avian influenza virus to other birds. Although only at the research stage, this breakthrough has potential to totally stop bird flu outbreaks spreading within poultry flocks.

Apart from the new gene to prevent virus spread, plus a marker gene to help researchers identify modified birds, these chickens are essentially the same as non-modified ISA browns. There is no observable difference in their development, health or growth, and they will even develop flu symptoms like normal birds.

Where they differ is that they cannot then pass the infection on to any other animals – chickens, wild birds or humans. The virus normally hijacks the host’s cell function to replicate itself – but in the GM birds, a special “decoy” molecule means that this cannot happen.

Apart from dramatically reducing the impact of an avian flu outbreak, this approach has the added advantage of being likely to work even if the virus mutates – a common cause of conventional vaccine resistance. In effect, a modified chicken and its offspring will not pass on any influenza with which it ever becomes infected. The downside is 100% of the flock in heavily-affected areas would need to be GM birds to guarantee total control of the disease.

Broad potential  

The technique could, theoretically be used to prevent replication in any Influenza A virus. The Influenza A group of viruses includes all significant influenzas of domesticated species. Dr Laurence Tiley, senior lecturer in molecular virology from the University of Cambridge, Department of Veterinary Medicine, explained that the research could pave the way for a preventative treatment for many other diseases such as Newcastle disease and infectious bursal disease and could be adapted for use in a wide range of domesticated animals such as ducks, turkeys and pigs. He stressed that the research birds are not destined for commercial production. It takes about 18 months to make a new transgenic line of birds. Once done, it would take around five years to expand this to production at a global scale, he added.

The most notorious avian influenza virus, the H5N1 virus subtype, first infected humans in 1997 during a poultry outbreak in Hong Kong SAR, China. Since then, it has spread from Asia to Europe and Africa and has become entrenched in poultry in some countries, resulting in millions of poultry infections, several hundred human cases, and many human deaths. Since 2003, there have been 320 human deaths attributed to bird flu, according to the World Health Organisation. According to WHO figures published on 11 April, the hardest hit countries have been Indonesia (145 deaths and 176 cases), Vietnam (59 deaths and 119 cases), and Egypt (46 deaths and 141 cases).

Dr Jon Lyall, lead author of the study from Cambridge's Department of Veterinary Medicine, said: "Avian influenza has had a devastating effect on poultry farmers in many parts of Asia and the Middle East. Experience has shown that the virus regularly jumps species from wild birds into chickens, and represents an ongoing problem despite the best efforts to prevent and contain these outbreaks. Replacing vulnerable chickens in such areas with birds that do not pass on the virus would have positive consequences for animal welfare, farmers' livelihoods and consumer safety."

Since bird flu can jump the gap between species, this development could not only protect the health of domestic poultry but could also reduce the risk of bird flu epidemics leading to new flu virus epidemics in the human population.

Countering any potential concerns over the possibility of the GM birds entering the food chain, Dr Tiley pointed out that the GM chickens are research birds, not intended for human consumption. He added that: "Chickens are potential bridging hosts that can enable new strains of flu to be transmitted to humans. Preventing virus transmission in chickens should reduce the economic impact of the disease and reduce the risk posed to people exposed to the infected birds."

Decoy  

The researchers modified the chickens to manufacture a small "decoy" molecule that mimics an important control element of the bird flu virus. The virus cannot reproduce itself because it tries to use the decoy molecule instead of its own viral genetic material in its replication process. When the transgenic chickens were infected with avian flu, they became sick but did not transmit the infection to other chickens kept in the same pen with them. This was the case even if the other chickens were normal (non-transgenic) birds.

Dr Tiley pointed out that the resistance mechanism will work against all strains of Influenza A, because they all have the same replication process. "We expect the decoy to work against all strains of avian influenza and that the virus will find it difficult to evolve to escape the effects of the decoy.

“This is quite different from conventional flu vaccines, which need to be updated in the face of virus evolution as they tend only to protect against closely matching strains of virus and do not always prevent spread within a flock."

Multiple benefits  

Professor Helen Sang, from The Roslin Institute at the University of Edinburgh, described the results as very encouraging. She added that: "Using genetic modification to introduce genetic changes that cannot be achieved by animal breeding demonstrates the potential of GM to improve animal welfare in the poultry industry. This work could also form the basis for improving economic and food security in many regions of the world where bird flu is a significant problem."

The study was funded by the Biotechnology and Biological Sciences Research Council. Professor Douglas Kell, BBSRC chief executive, said: "Infectious diseases of livestock represent a significant threat to global food security and the potential of pathogens, such as bird flu, to jump to humans and become pandemic has been identified by the government as a top level national security risk. The BBSRC funds world-class research to help to protect the UK from such eventualities and the present approach provides a very exciting example of novel approaches to producing disease-resistant poultry."