美国《科学》杂志10月10日发表了华裔科学家丁守伟教授新的抗病毒免疫机制研究成果,或有助于探寻抗病毒疫苗研制新路。
丁守伟自上世纪80年代起就从事RNA(核糖核酸)干扰研究。此前,他与其他科学家发现,RNA干扰介导的抗病毒免疫机制在植物、果蝇和线虫中发挥了主要作用。丁守伟等研究人员最新研究显示,哺乳动物同样会用RNA对抗病毒。
在接受新华社记者采访时,丁守伟介绍了这种抗病毒免疫机制的工作原理:它首先识别病毒的特异性双链RNA,然后将其切割成叫做小分子干扰RNA的片段,从而让病毒“失效”,不能再对人类等哺乳动物造成危害。在实验中,他们通过一种蚊子携带的病毒感染7天大的实验鼠进行研究,结果感染野生型病毒的实验鼠在5天后死亡,而去除抑制RNA干扰蛋白的变异株病毒在感染实验鼠后,会很快被清除,并同时产生多个小分子干扰RNA。
同一期《科学》杂志还发表了丁守伟与瑞士一个实验室合作的另一项研究,他们利用两种病毒感染未分化的小鼠胚胎干细胞,同样观察到了RNA抗病毒干扰机制。
“病毒极大地威胁着人类的健康。迄今对许多病毒造成的感染都没有行之有效的预防疫苗与治疗方法。我们和瑞士实验室分别利用不同的病毒感染哺乳动物,都发现了RNA干扰抗病毒免疫现象。基于此,我们相信,这是一种新的抗病毒免疫机制,”丁守伟说,“新发现弥补了当前人们对免疫反应认识上的空白,有可能为设计病毒疫苗开辟一个新的研究方向。”(生物谷Bioon.com)
生物谷推荐的英文摘要
Science DOI: 10.1126/science.1241911
RNA Interference Functions as an Antiviral Immunity Mechanism in Mammals
Yang Li1,*, Jinfeng Lu1,2,*, Yanhong Han1, Xiaoxu Fan1, Shou-Wei Ding1
Diverse eukaryotic hosts produce virus-derived small interfering RNAs (siRNAs) to direct antiviral immunity by RNA interference (RNAi). However, it remains unknown whether the mammalian RNAi pathway has a natural antiviral function. Here, we show that infection of hamster cells and suckling mice by Nodamura virus (NoV), a mosquito-transmissible RNA virus, requires RNAi suppression by its B2 protein. Loss of B2 expression or its suppressor activity leads to abundant production of viral siRNAs and rapid clearance of the mutant viruses in mice. However, viral small RNAs detected during virulent infection by NoV do not have the properties of canonical siRNAs. These findings have parallels with the induction and suppression of antiviral RNAi by the related Flock house virus in fruit flies and nematodes and reveal a mammalian antiviral immunity mechanism mediated by RNAi.
DOI: 10.1126/science.1241930
Antiviral RNA Interference in Mammalian Cells
P. V. Maillard1,*, C. Ciaudo1,*, A. Marchais1, Y. Li2, F. Jay1, S. W. Ding2, Olivier Voinnet1
In antiviral RNA interference (RNAi), the DICER enzyme processes virus-derived double-stranded RNA (dsRNA) into small interfering RNAs (siRNAs) that guide ARGONAUTE proteins to silence complementary viral RNA. As a counterdefense, viruses deploy viral suppressors of RNAi (VSRs). Well-established in plants and invertebrates, the existence of antiviral RNAi remains unknown in mammals. Here, we show that undifferentiated mouse cells infected with encephalomyocarditis virus (EMCV) or Nodamura virus (NoV) accumulate ~22-nucleotide RNAs with all the signature features of siRNAs. These derive from viral dsRNA replication intermediates, incorporate into AGO2, are eliminated in Dicer knockout cells, and decrease in abundance upon cell differentiation. Furthermore, genetically ablating a NoV-encoded VSR that antagonizes DICER during authentic infections reduces NoV accumulation, which is rescued in RNAi-deficient mouse cells. We conclude that antiviral RNAi operates in mammalian cells.