Abstract:
Viral infections activate pattern recognition receptors in the host, triggering an innate immune response that involves the production of interferons, which, in turn, stimulates the expression of antiviral effector genes. Viperin is one of the most highly induced interferon-stimulated genes and displays broad antiviral activity, especially against tick-borne viruses. Of late, camelid-borne zoonotic viruses have been on the rise in the Arabian Peninsula, but research into camelid antiviral effector genes has been limited. This is the first report of an interferon-responsive gene from the mammalian suborder Tylopoda to which modern camels belong. From camel kidney cells treated with dsRNA mimetic, we cloned viperin cDNA encoding 361 amino acid protein. Sequence analysis of camel viperin reveals high levels of amino acid conservation, particularly within the RSAD domain. Compared to kidney, the relative mRNA expression of viperin was higher in blood, lung, spleen, lymph nodes, and intestines. The in-vitro expression of viperin was induced by poly(I:C) and interferon treatment in camel kidney cell lines. Viperin expression was subdued in camel kidney cells infected with the camelpox virus during the early stages of infection, suggesting possible suppression by the virus. Overexpression of camel viperin through transient transfection significantly enhanced the resistance of cultured camel kidney cell lines to infection with camelpox virus. Research into the role of viperin in host immunity against emerging viral pathogens of camels will provide insight into novel mechanisms of antiviral activity of the protein, viral immune evasion strategies, and enable the development of better antivirals.
摘要:
病毒感染激活宿主的模式识别受体,引发涉及干扰素产生的先天免疫反应,which,反过来,刺激抗病毒效应基因的表达。Viperin是最高度诱导干扰素刺激的基因之一,并显示广泛的抗病毒活性,特别是对抗蜱病毒。迟到了,骆驼传播的人畜共患病毒在阿拉伯半岛呈上升趋势,但是对骆驼抗病毒效应基因的研究一直很有限。这是现代骆驼所属的哺乳动物Tylopoda亚目干扰素应答基因的首次报道。从用dsRNA模拟物处理的骆驼肾细胞中,我们克隆了viperincDNA,编码361个氨基酸的蛋白质。骆驼viperin的序列分析揭示了高水平的氨基酸保守性,特别是在RSAD域内。与肾脏相比,viperin在血液中的相对mRNA表达较高,肺,脾,脾淋巴结,和肠子。通过聚(I:C)和干扰素处理在骆驼肾细胞系中诱导viperin的体外表达。在感染的早期阶段,在感染骆驼痘病毒的骆驼肾细胞中,Viperin的表达受到抑制。暗示病毒可能会抑制。通过瞬时转染过表达骆驼viperin可显着增强培养的骆驼肾细胞系对骆驼痘病毒感染的抵抗力。研究viperin在宿主对新出现的骆驼病毒病原体的免疫中的作用将提供对蛋白质抗病毒活性的新机制的见解。病毒免疫逃避策略,并能够开发更好的抗病毒药物。