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蝙蝠 IRF1 在 IFN 诱导中的功能特征。

Functional characterization of bat IRF1 in IFN induction.

机构信息

Shanghai Key Laboratory of Veterinary Biotechnology, Key Laboratory of Urban Agriculture (South), Ministry of Agriculture, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai, China.

Shanghai Key Laboratory of Veterinary Biotechnology, Key Laboratory of Urban Agriculture (South), Ministry of Agriculture, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai, China.

出版信息

Dev Comp Immunol. 2022 Nov;136:104500. doi: 10.1016/j.dci.2022.104500. Epub 2022 Aug 3.

Abstract

Bats are natural hosts for various zoonotic viral diseases. However, they rarely show signs of disease infection with such viruses. During viral infection, members of the IRFs family induce the production of IFNβ and exert antiviral effects. However, the functions of bat interferon regulatory factors (IRFs) remain unclear. In this study, the Tadarida brasiliensis IRF1 (TbIRF1) gene was first cloned and a series of bioinformatics studies were conducted. Results showed that bat IRF1 protein sequence showed a low similarity with IRF1s from other species. RNA virus such as Newcastle disease virus (NDV-GFP), avian influenza virus (AIV) and vesicular stomatitis virus (VSV-GFP) infection of Tadarida brasiliensis 1 lung (TB 1 Lu) cells significantly promotes the expressions of IFNβ, PKR, and OAS1, and up-regulates the expression of TbIRF1. Overexpression of TbIRF1 markedly activates IFNβ promoter activity in a dose-dependent manner. Next, we constructed the TbIRF1 functional domain deletion plasmids and found that the DNA binding domain (DBD) is necessary for TbIRF1 to induce IFNβ expresison. In conclusion, the first bat IRF1 gene was cloned, and its functions in IFN induction were preliminarily identified.

摘要

蝙蝠是多种人畜共患病毒的天然宿主。然而,它们很少表现出感染此类病毒的疾病迹象。在病毒感染过程中,IRF 家族成员诱导 IFNβ 的产生并发挥抗病毒作用。然而,蝙蝠干扰素调节因子(IRF)的功能仍不清楚。在这项研究中,我们首次克隆了 Tadarida brasiliensisIRF1(TbIRF1)基因,并进行了一系列的生物信息学研究。结果表明,蝙蝠 IRF1 蛋白序列与其他物种的 IRF1s 相似度较低。新城疫病毒(NDV-GFP)、禽流感病毒(AIV)和水疱性口炎病毒(VSV-GFP)等 RNA 病毒感染 Tadarida brasiliensis1 肺(TB1Lu)细胞显著促进 IFNβ、PKR 和 OAS1 的表达,并上调 TbIRF1 的表达。TbIRF1 的过表达以剂量依赖性方式显著激活 IFNβ 启动子活性。接下来,我们构建了 TbIRF1 功能结构域缺失质粒,并发现 DNA 结合结构域(DBD)是 TbIRF1 诱导 IFNβ 表达所必需的。总之,我们首次克隆了蝙蝠 IRF1 基因,并初步鉴定了其在 IFN 诱导中的功能。

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