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刚地弓形虫致密颗粒蛋白-7(GRA-7)在体外和体内抑制病毒复制。

Dense Granule Protein-7 (GRA-7) of Toxoplasma gondii inhibits viral replication in vitro and in vivo.

机构信息

College of Veterinary Medicine, Chungnam National University, Daejeon, 34134, Republic of Korea.

Department of Molecular and Life Science, College of Science and Technology, Hanyang University, Ansan, 15588, Republic of Korea.

出版信息

J Microbiol. 2017 Nov;55(11):909-917. doi: 10.1007/s12275-017-7392-5. Epub 2017 Oct 27.

Abstract

Dense granule protein-7 (GRA-7) is an excretory protein of Toxoplasma gondii. It is a potential serodiagnostic marker and vaccine candidate for toxoplasmosis. Previous reports demonstrated that GRA-7 induces innate immune responses in macrophages by interacting with TRAF6 via the MyD88-dependent pathway. In the present study, we evaluated the antiviral activity and induction of an antiviral state by GRA-7 both in vitro and in vivo. It was observed that GRA-7 markedly reduced the replication of vesicular stomatitis virus (VSV-GFP), influenza A virus (PR8-GFP), coxsackievirus (H3-GFP), herpes simplex virus (HSV-GFP), and adenovirus-GFP in epithelial (HEK293T/HeLa) and immune (RAW264.7) cells. These antiviral activities of GRA-7 were attributed to the induction of type I interferon (IFN) signaling, resulting in the secretion of IFNs and pro-inflammatory cytokines. Additionally, in BALB/c mice, intranasal administration of GRA-7 prevented lethal infection by influenza A virus (H1N1) and exhibited prophylactic effects against respiratory syncytial virus (RSV-GFP). Collectively, these results suggested that GRA-7 exhibits immunostimulatory and broad spectrum antiviral activities via type I IFN signaling. Thus, GRA-7 can be potentially used as a vaccine adjuvant or as a candidate drug with prophylactic potential against viruses.

摘要

致密颗粒蛋白-7(GRA-7)是刚地弓形虫的一种分泌蛋白。它是弓形虫病潜在的血清学诊断标志物和疫苗候选物。先前的报告表明,GRA-7 通过 MyD88 依赖性途径与 TRAF6 相互作用,诱导巨噬细胞固有免疫反应。在本研究中,我们评估了 GRA-7 在体外和体内的抗病毒活性和诱导抗病毒状态的能力。结果表明,GRA-7 显著降低了上皮细胞(HEK293T/HeLa)和免疫细胞(RAW264.7)中水泡性口炎病毒(VSV-GFP)、甲型流感病毒(PR8-GFP)、柯萨奇病毒(H3-GFP)、单纯疱疹病毒(HSV-GFP)和腺病毒-GFP 的复制。GRA-7 的这些抗病毒活性归因于诱导 I 型干扰素(IFN)信号,导致 IFN 和促炎细胞因子的分泌。此外,在 BALB/c 小鼠中,鼻内给予 GRA-7 可预防甲型流感病毒(H1N1)的致死性感染,并对呼吸道合胞病毒(RSV-GFP)表现出预防作用。综上所述,这些结果表明,GRA-7 通过 I 型 IFN 信号发挥免疫刺激和广谱抗病毒活性。因此,GRA-7 可作为疫苗佐剂或具有预防病毒作用的候选药物。

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