Highly differentiated cultures of ferret airway epithelium for the study of respiratory viruses, including influenza.

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To study the transmission of a virus from one host to another, the use of whole animals is ultimately unavoidable. However we can strive to make sure that the numbers of animals that are used are minimized and that the whole animal studies are complemented by the very best research in vitro. In that way, the answers gained from the whole animal studies tell a complete story and move the field on. We aim to understand why some influenza viruses transmit between people whilst others do not. This allows us to predict how and when influenza pandemics will arise. We use ferrets to achieve this. One ferret is infected with a known dose of virus and another animal is exposed to see if they catch the virus. This can tell us which viruses transmit but not why. Moreover many different strains of virus might be tested at many different doses before the right conditions for the experiment are found. Here we propose to develop a sophisticated cell culture model using the very same target cells as become infected in the animal, the cells of the nose and throat. In this way we can recapitulate in a test tube the environment the virus has to cope with in real life. What is more, from a single animal we can reproduce more than 50 equivalent test tube cultures to test different viruses side by side and look at the effects of drugs and other interventions on the virus.Because the ferret and human respiratory system are similar, we predict that these ferret airway cultures will be useful for studying other human respiratory diseases.