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翻译后修饰在IFITM蛋白抗病毒功能中的作用及机制研究

批准号81571988 学科分类病毒、病毒感染与宿主免疫 ( H1904 )
项目负责人乔文涛 负责人职称教授 依托单位南开大学
资助金额60.00
万元
项目类别面上项目 研究期限2016 年 01 月 01 日 至
2019 年 12 月 31 日
中文主题词干扰素诱导穿膜蛋白;翻译后修饰;抗病毒活性
英文主题词interferon-induced transmembrane proteins;post-translational modifications;the antiviral activity

摘要

中文摘要 干扰素诱导穿膜蛋白(interferon-induced transmembrane proteins,IFITMs)可抑制包括流感病毒(IAV)、丙肝病毒(HCV)及人类免疫缺陷病毒(HIV-1)在内多科属病毒的入胞过程,在宿主抗病毒防御中发挥重要作用。对其抗病毒机制的深入研究,可为研发以IFITMs为基础的广谱抗病毒手段提供理论支撑。前期研究表明,正确的翻译后修饰对IFITM3及IFITM1行使抗病毒功能非常重要。本项目拟以此为切入点,明确已知修饰对IFITM3及IFITM1生物学性质(如量、运输与定位)及抗病毒活性的影响及调控机制,分析参与IFITMs翻译后修饰的关键酶等协同完成抗病毒功能的细胞蛋白,并初探作用机制。本项目工作有助进一步认识IFITMs抗病毒过程的分子细节,发现干预病毒入胞过程的可能靶点,为深入理解病毒与宿主防御间博弈关系提供理论依据。
英文摘要 IFITMs (interferon-induced transmembrane proteins) inhibit the entry of many viruses, including influenza A virus (IAV), hepatitis C virus (HCV), and human immunodeficiency virus type 1 (HIV-1), etc. This broad antiviral activity indicates an important role of IFITM proteins in host antiviral defense, and also suggests the possibility of developing IFITM-based approaches to curb the pandemics that are caused by the aforementioned human pathogenic viruses. The previous studies showed that the proper post-translational modifications are indispensable for the antiviral activity of IFITMs, even though they have different antiviral spectrums. On the basis of these published data, this project is aimed to define the functions and mechanisms of post-translational modifications in IFITM3 and IFITM1 biological properties (amount, traffic and localization) and antiviral activity. Besides, we also plan to identify the key enzymes for post-translational modifications and other host cofactors of IFITMs and investigate the mechanisms. Collectively, these data will help us further understand the detail mechanisms of IFITMs antiviral activity, and find a potential target for interfering viral entry. Furthermore, this study may yield evidence for insight into the balance between virus and host defense.
结题摘要

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