Developing an in vitro approach to study transmission of respiratory viruses.

流感是一种高度传染性的疾病，通过空气将病毒从一个感染者传播到新的宿主。许多不同的流感病毒存在于动物体内，偶尔会交叉感染人类，引起暴发或大流行。动物流感病毒只有通过空气在人类之间有效传播才能引起大流行。我们目前还不明白为什么有些动物病毒可以做到这一点，而另一些则不行。研究这种宿主范围障碍的一种方法是使用动物模型，如雪貂。雪貂可以感染许多不同的人类和动物流感病毒株，但似乎只有已经适应人类的病毒才能通过空气从一只受感染的雪貂传播到另一只关在隔壁笼子里的动物。大量使用雪貂模型的工作正在出现，并为该领域提供了信息，但该模型远非理想。一个特别的问题是，只使用了少量的动物，这使得很难测量不同病毒传播效率之间的微小差异，即使这些微小差异可能解释重要的流行病学影响。这个问题可以通过使用更多的动物来解决。然而，在这里，我们提出了一种替代策略，它将减少使用的动物数量，因为它将用细胞培养系统取代其中的许多动物。这些培养物由上呼吸道靶组织中存在的不同类型的人类细胞组成。如果病毒成功地通过空气超过一定距离，细胞就会被感染，并且可以通过粘液层（如覆盖在人类鼻子和喉咙上的粘液层）开始感染。重要的是，该系统将允许我们测量一只受感染动物的传染时间长度。这个传染期对病毒在社区的传播有很大的影响，是公共卫生规划者需要了解的一个重要参数。最终，我们建议我们的系统可以用来测量人类的这个参数。一旦我们用少量受感染的雪貂验证和校准了系统，我们将开始比较不同病毒株的传染性长度，以更多地了解动物病毒引起人类疫情的可能性。在项目后期，我们建议用细胞培养完全取代少量的雪貂。它们会被病毒感染，经过它们的空气会模仿人类的正常呼吸。这将使我们能够测量通过呼吸道传播的其他重要人类病毒的一些传播参数，如腮腺炎，B型流感病毒和副流感病毒。最终，我们希望了解传播将有助于我们更适当地使用干预措施来控制呼吸道病毒的传播。

Influenza is a highly contagious disease that is spread by the transmission of virus through the air from one infected person to a new host. Many different influenza viruses are present in animals and occasionally these cross over into humans and cause outbreaks or pandemics. Animal influenza viruses can only cause pandemics if they spread efficiently between humans by passing through the air. We do not currently understand why some animal viruses can do this and others don't. One way to study this host range barrier is to use animal models such as ferrets. Ferrets can be infected with many different strains of human and animal influenza viruses but only the viruses that are already adapted to humans seem to pass through the air from one infected ferret to another animal housed in the next cage. A large body of work using the ferret model is emerging and informing the field but the model is far from ideal. One particular problem is that only small numbers of animals are used, and this makes it difficult to measure small differences between the transmission efficiency of different viruses, even though these small differences might account for important epidemiological effects. The problem might be solved by using many more animals. However here we propose an alternative strategy which will reduce the numbers of animals used because it will replace many of them with cell culture systems. These cultures are made up of different types of human cells that are present in the target tissue of the upper respiratory tract. The cells will become infected if the virus successfully passes through the air over a certain distance and can initiate infection through a mucus layer such as the one that coats the human nose and throat. Importantly the system will allow us to measure the length of time over which one infected animal is contagious. This contagiousness period can have a very large impact on the spread of a virus through the community and is an important parameter for public health planners to know. Eventually we propose that our system could be used to measure this parameter in humans. Once we have validated and calibrated the system using a small number of infected ferrets, we will begin to compare the length of contagiousness of different strains of virus to understand more about the likelihood that animal viruses will cause human outbreaks. Later in the project we propose to completely replace even the small number of ferrets with cell cultures. These will be infected with virus and air passing over them will mimic the normal breathing of a human. This will allow us to measure some transmission parameters of other important human viruses that spread through the respiratory route such as mumps, influenza type B and parainfluenza viruses. Ultimately we hope that understanding transmission will help us to use interventions more appropriately to control the spread of respiratory viruses.