权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Prenylation in antiviral immunity

抗病毒免疫中的异戊二烯化

基本信息

批准号：
10647533
负责人：
Ram Savan
金额：
$ 64.66万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-02-14 至 2028-01-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10647533
关键词：
Antiviral Response Genes Interferons Location NFIB gene Play Virus Diseases antiviral immunity insight novel prenylation

项目摘要

Summary In this proposal, we will explore the role of prenylation in antiviral immunity. Prenylation is a post-translational modification that renders proteins hydrophobic, thus targeting them to the endomembrane. While the role of prenylation in immunity is unclear, our preliminary data shows compelling evidence that prenylation is a modification widely used in innate antiviral immunity. As both the host and virus utilize prenylation and the cholesterol biosynthetic pathway, we propose a dynamic host-pathogen interaction at this interface. We hypothesize that prenylation could be a potent host innovation to counter viral pathogenesis. This is based on in silica analysis that revealed an enrichment of immunity-related proteins with a prenylation motif. We followed in-silica analyses with a biochemical screen and identified several prenylated antiviral proteins that are involved in interferon responses and virus restriction, with potential to affect virus entry, replication, and egress. In this grant, we propose to identify the functional consequences of prenylated proteins on subcellular localization, interferon signaling, and antiviral function. By perturbing specific enzymes in the prenylation pathway, we will study its effect on interferon response, antiviral effectors, and virus control. This work will provide novel insights into cell-intrinsic antiviral countermeasures and the development of novel antiviral drug targets.

总结在这个提议中，我们将探讨异戊二烯化在抗病毒免疫中的作用。异戊烯化是一种翻译后使蛋白质疏水的修饰，从而使它们靶向内膜。虽然作用尽管免疫中的异戊烯化作用尚不清楚，但我们的初步数据显示，有令人信服的证据表明，异戊烯化是一种修饰广泛用于先天性抗病毒免疫。由于宿主和病毒都利用异戊二烯化，胆固醇生物合成途径，我们提出了一个动态的主机-病原体在这个接口的相互作用。我们假设异戊烯化可能是对抗病毒发病机制有效的宿主创新。这是基于在二氧化硅分析中，其揭示了具有异戊烯基序的免疫相关蛋白的富集。我们随后进行了生物化学筛选的二氧化硅分析，并鉴定了几种异戊二烯化的抗病毒蛋白，参与干扰素应答和病毒限制，可能影响病毒进入、复制和出口在这项研究中，我们建议确定异戊二烯化蛋白质对亚细胞的功能影响，定位、干扰素信号传导和抗病毒功能。通过干扰异戊烯化反应中的特定酶途径，我们将研究其对干扰素应答，抗病毒效应和病毒控制的影响。这项工作将为细胞内在抗病毒对策和新型抗病毒药物的开发提供了新的见解目标的