重症流感（如H7N9与H5N1）感染可诱导高水平炎症因子应答，但干扰素应答较低甚至缺失。病毒如何逃逸宿主干扰素通路的抑制作用尚未得到阐明。本研究从两条思路入手：一是以传统的模式识别受体及信号通路的调控为切入点，以体内肺组织原位观察病毒对信号通路的调控作用以及体内干扰特定靶标分子为主要手段，结合体外细胞模型进行验证，了解重症流感病毒对干扰素通路上的三个环节的是否均存在逃逸及其机制；二是探索重症流感感染是否启动宿主应急机制、或者感染导致的缺氧启动宿主应急机制、从而导致宿主产生高炎症因子应答，这一机制中表观调控起着决定性作用。这些机制的阐明为新药与免疫干预技术提供新的可能靶点。

Severe Influenza infection usually is associated with hypercytokinemia, but the type I Interferon remains at low lever or absence. The regulatory mechanism on type I interferon by virus remains to be determined. We plan to explore two different approaches to unfold the underlying mechanism. First, we will investigate the traditional pattern recognition receptors and their signaling pathways, and determine how viral products will cause the unbalanced immune responses with preferentially up-regulating inflammatory cytokines but not type I interferon. The investigation will be performed on the lung tissues with a combo of technologies, including in situ hybridization and immunofluorescence staining and in situ interference with siRNA. In combination with in vitro experiments on cell lines, observations from these experiments will allow us to understand whether influenza virus are capable of attacking various targets in the IFN signaling pathway. Second, we will determine whether influenza is able to initiate an “emergence mode” or this mechanism is only initiated during hypoxia which could be resulted from the inflammation of lung by infection. Our studies may identify more targets for new drug development or immune intervention.