Dynamic Control of Innate Antiviral Immunity in Skin Homeostasis and Inflammation

项目摘要 先天性抗病毒蛋白（如OAS2和OASL）的功能缺失突变和抑制与高表达相关。 小鼠和人类的病毒感染率。由于它们受干扰素的诱导，这些抗病毒蛋白通常是 被称为干扰素刺激基因（ISG）。虽然重组干扰素刺激这些抗病毒药物的产生， 虽然I型干扰素是一种蛋白质，但其严重的毒性是其治疗效用的主要限制。此外，药理学 抗病毒药物，如无环鸟苷，在脆弱的患者中具有引发中性粒细胞减少和肾毒性的高风险 人口。因此，对于新的抗病毒治疗剂存在显著的未满足的临床需求。这种需要可以是 通过发展对内源性抗病毒蛋白的干扰素非依赖性调节的充分理解来解决， 通过激活这种极其有效的天然抗病毒途径来确定治疗和预防的靶点。我们 拟议的工作将回答重要的问题：1）哪些干扰素独立的信号和途径可以诱导 抗病毒能力？2)上皮抗病毒天然免疫在单细胞水平上是否不同？3)哪些因素 协同诱导先天性抗病毒免疫

Project Summary Loss-of-function mutations and suppression of innate antiviral proteins, such as OAS2 and OASL are associated with high viral infection rates in mice and humans. Because of their induction by interferons, these antiviral proteins are often referred to as interferon-stimulated genes (ISG). While recombinant interferon stimulates production of these antiviral proteins, type I interferon’s severe toxicity is the major limitation in its therapeutic utility. Additionally, pharmacological antivirals, such as acyclovir, have a high risk for triggering neutropenia and nephrotoxicity in vulnerable patient populations. Therefore, there is a significant unmet clinical need for new antiviral therapeutics. This need can be addressed by developing a full understanding of interferon-independent regulation of endogenous antiviral proteins and identifying targets for therapy and prevention by activation of this incredibly potent natural antiviral pathway. Our proposed work will answer important question: 1) Which interferon-independent signals and pathways can induce antiviral competence? 2) Does epithelial antiviral innate immunity differ on a single cell level? 3) What factors collaborate in the induction of innate antiviral immunity?