Molecular identification and antiviral function of the guanylate-binding protein (GBP) genes in the Chinese tree shrew (Tupaia belangeri chinesis)

Molecular identification and antiviral function of the guanylate-binding protein (GBP) genes in the Chinese tree shrew (Tupaia belangeri chinesis)
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中国树鼩鸟苷酸结合蛋白(GBP)基因的分子鉴定及其抗病毒功能

DOI:
10.1016/j.dci.2019.02.014
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发表时间:
2019-07-01
影响因子:
2.9
通讯作者:
Yao, Yong-Gang
Yao, Yong-Gang
中科院分区:
生物学3区
文献类型:
--
作者:
Gu, Tianle;Yu, Dandan;Yao, Yong-Gang

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在病毒检测和干扰素(IFN)产生后,数百个干扰素刺激基因(ISGs)随后被诱导作为直接抗病毒效应器或干扰素信号调节因子。鸟苷结合蛋白(GBP)家族属于干扰素诱导的GTP酶,保护宿主免受寄生虫、细菌和病毒等多种入侵病原体的侵袭。树鼠(Tupaia Belangeri Chinese)越来越多地被用作研究病毒性传染病的灵长类动物的替代实验动物。到目前为止,树鼠GBP家族还没有被描述出来。在本研究中,我们克隆了5个树鼠GBP基因(tGBP1、tGBP2、tGBP4、tGBP5和tGBP7),并对它们的抗病毒活性进行了研究。这些TGBPs在树鼠的心、脾、肠、肾、肝、肺和脑组织中广泛表达。树鼠原代肾细胞(TSPRC)经干扰素-γ处理后,tGBPs的mRNA表达明显增强。新城疫病毒(NDV)、脑心肌炎病毒(EMCV)和1型单纯疱疹病毒(HSV-1)感染后,TSPRCs的tGBPs基因表达增强,但TGBP蛋白在胞浆内的定位无明显变化。TGBP1对水疱性口炎病毒(VSV)和单纯疱疹病毒1型(HSV-1)感染显示出抗病毒活性,而其他四种TGBP则不显示。综上所述,本研究为树鼠GBP家族成员的研究提供了第一手资料,为树鼠传染病动物模型的建立提供了可能。
Following viral detection and interferons (IFNs) production, several hundreds of IFN-stimulated genes (ISGs) are subsequently induced to act as direct antiviral effectors or regulators of the IFN signaling. The guanylate-binding protein (GBP) family belongs to IFN-inducible GTPases defending the host against a diverse group of invading pathogens such as parasites, bacteria and viruses. The Chinese tree shrew (Tupaia belangeri chinese) has been increasingly used as an alternative experimental animal to primates in studying viral infectious diseases. Hitherto, the tree shrew GBP family has not been characterized. In this study, we identified five tree shrew GBP genes (tGBP1, tGBP2, tGBP4, tGBP5 and tGBP7) and characterized their antiviral activities. All these tGBPs were ubiquitously expressed in heart, spleen, intestines, kidney, liver, lung and brain tissues of the tree shrew. IFN-gamma treatment of tree shrew primary renal cells (TSPRCs) significantly induced the mRNA expression of tGBPs. Infections with Newcastle disease virus (NDV), encephalomyocarditis virus (EMCV) and type 1 herpes simplex virus (HSV-1) enhanced tGBPs mRNA expression in TSPRCs, but had no effect on the localization of tGBP proteins in the cytoplasm. tGBP1, but not the other four tGBPs, showed antiviral activity against vesicular stomatitis virus (VSV) and HSV-1 infections. Taken together, this study provided the first-hand information of the GBP family members in the Chinese tree shrew, which might assist the development of tree shrew animal model for infectious diseases.