Identification of cellular genes that affect host range restriction of influenza virus

流感病毒对人类健康构成大流行威胁，因为禽流感病毒有时可以获得在人与人之间复制和传播的能力。由于人类对这些毒株没有预先免疫力，整个世界都易受感染，病毒迅速传播，造成过高的发病率和死亡率。这种情况可能发生的方式是禽流感病毒在其基因组成中获得突变，这有助于它在人类细胞中更快地复制。我们知道实现这种转换的一些突变，但我们不了解它们背后的机制。在这个项目中，我们将从鸡和人类宿主中鉴定基因，这可能是确定特定病毒是否可以在任何一个宿主中复制的重要基因。然后我们将设计实验来发现为什么它们对流感病毒复制很重要。这些基本的科学信息将使我们了解如何预测哪些病毒株最有可能引起大流行，并将有助于设计针对病毒周期关键步骤的新型抗病毒化合物。

Influenza viruses pose a pandemic threat to human health because avian influenza viruses can sometimes acquire the ability to replicate in and transmit between people. Since humans have no pre-existing immunity to these strains, the whole world is susceptible and the virus spreads rapidly causing excess morbidity and mortality. The way in which this might happen is for a strain of bird flu to acquire a mutation in its genetic makeup that helps it replicate faster in human cells. We know about some of the mutations by which this switch is achieved, but we do not understand the mechanism behind them. In this project we will identify genes from the chicken and from the human host which might be important in determining whether a particular virus can replicate in either host. Then we will design experiments to discover why they are important for influenza virus replication. This basic scientific information will allow us to understand how to predict which strains of virus are the ones most likely to cause pandemics, and will also assist design of novel antiviral compounds that target essential steps of the virus cycle.