Investigating the function and regulation of IFITM proteins in interferon biology and disease

干扰素诱导跨膜蛋白(IFITM)基因家族由三个抗病毒限制因子IFITM1-3组成。从2009年开始的研究表明，这些蛋白在各种感染模型中具有关键的和广谱的保护活性，通过防止衣壳融合而作用于病毒进入水平。然而，理查德·斯隆和凯瑟琳·鲍尔实验室的研究揭示了这些蛋白质的新功能。斯隆实验室已经证明，IFITM蛋白通过抑制病毒蛋白翻译，独立于病毒进入步骤抑制细胞内HIV1病毒的产生。鲍尔实验室还独立发现了IFITM1和IFITM3在调节干扰素诱导的细胞蛋白质合成中的作用。我的目标是澄清IFITM生物学的这一新方面，详细说明它是如何被翻译后修饰调控的，并研究对疾病情景的影响。

The Interferon Induced Transmembrane (IFITM) gene family consists of three anti-viral restriction factors, IFITM1-3. Studies starting in 2009 demonstrated that these proteins have critical and broad-spectrum protective activities in a variety of infection models, acting at the level of viral entry by preventing capsid fusion. Research from the laboratories of Richard Sloan and Kathryn Ball however have revealed novel functions for these proteins. The Sloan lab has shown that IFITM proteins inhibit intracellular HIV1 virus production independently of the viral entry step by inhibiting viral protein translation. The Ball lab have also independently discovered a role for IFITM1 and IFITM3 in regulating interferon-induced cellular protein synthesis. My goal is to clarify this new aspect of IFITM biology, detail how it is regulated by post-translational modification, and study implications for disease scenarios.