美国匹兹堡大学医学院Saumendra N. Sarkar团队近期取得重要工作进展，他们研究提出，典型抗病毒蛋白寡腺苷酸合成酶1通过增强IRF1翻译发挥抗菌功能。相关研究成果2024年7月1日在线发表于《免疫》杂志上。

据介绍，微生物感染期间宿主先天免疫反应的一个重要特性是其控制抗微生物效应蛋白表达的能力，但这是如何在转录后发生的尚不清楚。

研究人员描述了经典抗病毒基因2′-5′-寡腺苷酸合成酶1（OAS1）的关键抗菌作用。人OAS1及其小鼠直系同源物Oas1b由干扰素-γ诱导，并在体外和体内保护其免受胞质细菌病原体（如新弗朗西斯杆菌和单核细胞增多性李斯特菌）的侵害。蛋白质组学和转录组学分析显示，在OAS1缺陷细胞中IRF1蛋白表达减少。从机制上讲，OAS1将IRF1 mRNA结合并定位于粗糙内质网（ER）-高尔基体内膜，允许IRF1 mRNA的有效翻译，而不影响其转录或衰变。IRF1的OAS1依赖性翻译导致限制细胞内细菌的抗菌效应物（如GBP）的表达增强。

总之，这些发现揭示了OAS1在抗菌先天免疫中的非经典功能。

附：英文原文

Title: The canonical antiviral protein oligoadenylate synthetase 1 elicits antibacterial functions by enhancing IRF1 translation

Author: Munesh K. Harioudh, Joseph Perez, Lomon So, Mayank Maheshwari, Thomas S. Ebert, Veit Hornung, Ram Savan, A. Rouf Banday, Michael S. Diamond, Vijay A. Rathinam, Saumendra N. Sarkar

Issue&Volume: 2024-07-01

Abstract: An important property of the host innate immune response during microbial infectionis its ability to control the expression of antimicrobial effector proteins, but howthis occurs post-transcriptionally is not well defined. Here, we describe a criticalantibacterial role for the classic antiviral gene 2′-5′-oligoadenylate synthetase1 (OAS1). Human OAS1 and its mouse ortholog, Oas1b, are induced by interferon-γ andprotect against cytosolic bacterial pathogens such as Francisella novicida and Listeria monocytogenes in vitro and in vivo. Proteomic and transcriptomic analysis showed reduced IRF1 protein expression inOAS1-deficient cells. Mechanistically, OAS1 binds and localizes IRF1 mRNA to the roughendoplasmic reticulum (ER)-Golgi endomembranes, licensing effective translation ofIRF1 mRNA without affecting its transcription or decay. OAS1-dependent translationof IRF1 leads to the enhanced expression of antibacterial effectors, such as GBPs,which restrict intracellular bacteria. These findings uncover a noncanonical functionof OAS1 in antibacterial innate immunity.

DOI: 10.1016/j.immuni.2024.06.003

Source: https://www.cell.com/immunity/abstract/S1074-7613(24)00309-1