鸡干扰素诱导跨膜蛋白1抑制新城疫病毒感染的分子机制

新城疫病毒（NDV）是严重危害家禽养殖业的病原体，宿主因子在NDV感染中的作用所知甚少。干扰素诱导跨膜蛋白（IFITMs）是一种抗病毒因子，能够限制多种通过内吞途径入侵细胞的囊膜病毒的进入过程。我们前期研究发现，鸡IFITM1（chIFITM1）在NDV感染后上调表达，表明其可能参与NDV的感染过程。本项目拟首先分析chIFITM1与干扰素介导的抗NDV活性的相关性；然后通过检测chIFITM1和NDV在细胞中的定位分布，并探索chIFITM1对NDV在以直接膜融合和内吞途径入侵的细胞中的复制以及NDV感染具体阶段的影响，以明确chIFITM1参与NDV感染的具体途径；最后通过确定NDV膜融合的发生位点，并鉴定chIFITM1影响NDV膜融合的具体阶段，以揭示chIFITM1影响NDV感染入侵过程的作用机制。本项目期望阐明chIFITM1介导的干扰素抗NDV活性的分子机制。

Newcastle disease virus (NDV) is an important pathogen which causes serious threats to the poultry industry; the contributions of host factors during the course of NDV infection remain largely unknown. The interferon-inducible transmembrane (IFITM) represents a kind of cellular antiviral factors that can block entry stages of diverse enveloped viruses which entry cell via endocytosis. We previously demonstrated that chIFITM1 was up-regulated during NDV infection, indicating this factor maybe involve in the infection process of NDV. In this proposal, we intend to examine the correlation between chIFITM1 and the anti NDV activity mediated by interferon. Then, the subcellular localization of chIFITM1 and NDV in cells will be determined, and the effects of chIFITM1 on the replication of NDV in cells which NDV entry through direct membrane fusion and endocytosis; as well as the effects of chIFITM1 on the specific stage of NDV infection will be examined. Based on the results above, we attempt to identify the specific ways of chIFITM1 to participate in the infection process of NDV. Finally, the site of NDV membrane fusion will be identified and the effects of chIFITM1 on the specific step of NDV membrane fusion will be investigated to elucidate the mechanisms of the effect of chIFITM1 on the invasion process of NDV. This project expects to elucidate the molecular mechanism of chIFITM1 mediated anti NDV activity of interferon.