美國(guó)《科學(xué)》雜志10月10日發(fā)表了華裔科學(xué)家丁守偉教授新的抗病毒免疫機(jī)制研究成果,，或有助于探尋抗病毒疫苗研制新路。
丁守偉自上世紀(jì)80年代起就從事RNA（核糖核酸）干擾研究,。此前，他與其他科學(xué)家發(fā)現(xiàn)，RNA干擾介導(dǎo)的抗病毒免疫機(jī)制在植物、果蠅和線蟲中發(fā)揮了主要作用,。丁守偉等研究人員最新研究顯示，哺乳動(dòng)物同樣會(huì)用RNA對(duì)抗病毒,。
在接受新華社記者采訪時(shí)，丁守偉介紹了這種抗病毒免疫機(jī)制的工作原理：它首先識(shí)別病毒的特異性雙鏈RNA,，然后將其切割成叫做小分子干擾RNA的片段,，從而讓病毒“失效”，不能再對(duì)人類等哺乳動(dòng)物造成危害,。在實(shí)驗(yàn)中,，他們通過一種蚊子攜帶的病毒感染7天大的實(shí)驗(yàn)鼠進(jìn)行研究，結(jié)果感染野生型病毒的實(shí)驗(yàn)鼠在5天后死亡,，而去除抑制RNA干擾蛋白的變異株病毒在感染實(shí)驗(yàn)鼠后,，會(huì)很快被清除，并同時(shí)產(chǎn)生多個(gè)小分子干擾RNA,。
同一期《科學(xué)》雜志還發(fā)表了丁守偉與瑞士一個(gè)實(shí)驗(yàn)室合作的另一項(xiàng)研究,，他們利用兩種病毒感染未分化的小鼠胚胎干細(xì)胞，同樣觀察到了RNA抗病毒干擾機(jī)制,。
“病毒極大地威脅著人類的健康,。迄今對(duì)許多病毒造成的感染都沒有行之有效的預(yù)防疫苗與治療方法。我們和瑞士實(shí)驗(yàn)室分別利用不同的病毒感染哺乳動(dòng)物,，都發(fā)現(xiàn)了RNA干擾抗病毒免疫現(xiàn)象,。基于此,，我們相信,，這是一種新的抗病毒免疫機(jī)制，”丁守偉說,，“新發(fā)現(xiàn)彌補(bǔ)了當(dāng)前人們對(duì)免疫反應(yīng)認(rèn)識(shí)上的空白,，有可能為設(shè)計(jì)病毒疫苗開辟一個(gè)新的研究方向。”（生物谷Bioon.com）
生物谷推薦的英文摘要
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.
