University of Cambridge > > Immunology in Pathology > Burning bridges. Transgenic approaches to eliminate the intermediate hosts of pandemic influenza.

Burning bridges. Transgenic approaches to eliminate the intermediate hosts of pandemic influenza.

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Host: Adrian Kelly (

Avian influenza (AIV) is a serious and on-going threat to human food security. It is also the fundamental source of all new strains of influenza virus that threaten to emerge in humans with pandemic consequences (such as H5N1 and H7N9 ).

The natural reservoir of AIV is in wild shorebirds and waterfowl. Transmission to domesticated livestock species (e.g chickens, ducks and pigs) has substantial economic impact. These hosts also act as intermediates that facilitate virus amplification and adaptation that can increase the likelihood of cross-species transmission to humans. The emergence of new pandemic strains of influenza is probably inevitable. The impact of such pandemics is largely down to luck, despite our efforts to increase our pandemic preparedness. A great deal of effort over the past 15 years has been directed at increasing global surveillance, developing improved vaccines and antiviral drugs so that the next pandemic can be detected and responded to as rapidly and effectively as possible. The failure to contain the 2009 H1N1 pandemic is a sobering benchmark of our success so far.

The central role of the intermediate “bridging hosts” provides us with an opportunity to reduce the likelihood of a new pandemic strain emerging in the first place. Preventing contact between the AIV reservoir and large populations of susceptible hosts would achieve this. Nothing practical can be done about the natural reservoir. However, there are a number of things that can be done about the bridges. One radical approach is to remove them from the equation by using a range of genetic modification (GM) approaches to make them genetically resistant to AIV . We have introduced a transgene that produces a short RNA hairpin “decoy” molecule that binds specifically to the influenza virus polymerase and disrupts its activity. Chickens carrying the decoy were still susceptible to infection by AIV , but were prevented from transmitting the infection on to sentinel chickens placed in direct contact with them (even if these sentinels were non-transgenic). The transgene is stably integrated into the chicken genome with no detrimental consequences and is active across multiple generations. This is a promising first step towards producing chickens that no longer act as bridging hosts for AIV .

We hope that our work will raise public awareness in favour of the potential of GM for controlling serious infectious disease in livestock, particularly where these infections pose a major risk to public health and food security.

This talk is part of the Immunology in Pathology series.

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