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