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

为了研究病毒从一个宿主到另一个宿主的传播，使用整个动物最终是不可避免的。然而，我们可以努力确保使用的动物数量最少，并且整个动物研究都得到最好的体外研究的补充。通过这种方式，从整个动物研究中获得的答案讲述了一个完整的故事，并推动了该领域的发展。我们的目标是了解为什么有些流感病毒会在人与人之间传播，而另一些则不会。这使我们能够预测流感大流行将如何以及何时出现。我们用雪貂来达到这个目的。一只雪貂感染了已知剂量的病毒，另一只动物暴露在环境中，看它们是否感染了病毒。这可以告诉我们哪种病毒传播，但不能告诉我们为什么传播。此外，在找到合适的实验条件之前，可能会对许多不同的病毒株进行许多不同剂量的测试。在这里，我们建议开发一种复杂的细胞培养模型，使用在动物中感染的相同靶细胞，即鼻子和喉咙的细胞。通过这种方式，我们可以在试管中重现病毒在现实生活中必须应对的环境。更重要的是，我们可以从一只动物身上复制出50多个等效的试管培养物，以并排测试不同的病毒，并观察药物和其他干预措施对病毒的影响。由于雪貂和人类呼吸系统相似，我们预测这些雪貂气道培养物将有助于研究其他人类呼吸系统疾病。

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.