5’非翻译区条形码揭示2019新型冠状病毒毒力  

5’ UTR Barcode of the 2019 Novel Coronavirus Leads to Insights into Its Virulence

作　　者：段广有[1,2] 施劲松 宣益波 陈嘉源 刘畅 阮吉寿[6] 高山[1] 李鑫[1] DUAN Guangyou;SHI Jinsong;XUAN Yibo;CHEN Jiayuan;LIU Chang;RUAN Jishou;GAO Shan;LI Xin(College of Life Sciences,Nankai University,Tianjin 300071,China;School of Life Sciences,Qilu Normal University,Jinan 250200,China;National Clinical Research Center of Kidney Disease,Jinling Hospital,Nanjing University School of Medicine,Nanjing 210016,China;College of Life Sciences,Hebei Normal University,Shijiazhuang 050024,China;School of Medicine,Nankai University,Tianjin 300071,China;School of Mathematical Sciences,Nankai University,Tianjin 300071,China)

机构地区：[1]南开大学生命科学学院,天津300071 [2]齐鲁师范学院生命科学学院,济南250200 [3]东部战区总医院,南京210016 [4]河北师范大学生命科学学院,石家庄050024 [5]南开大学医学院,天津300071 [6]南开大学数学科学学院,天津300071

出　　处：《病毒学报》2020年第3期365-370,共6页Chinese Journal of Virology

摘　　要：2019年12月,中国武汉报道了2019新型冠状病毒(2019 novel coronavirus,2019-nCoV)引起的肺炎。在前期研究中,我们在国际上首次报道了有关2019-nCoV的两个重要发现:①Beta冠状病毒B亚群存在大量的可变翻译;②2019-nCoV的S蛋白可能存在Furin蛋白酶切位点。本研究在国际上首次报道了2019-nCoV的5’非翻译区分析的结果:Beta冠状病毒可以根据其5’非翻译区条形码分为不同毒力的四个类;这四类对应Beta冠状病毒的四个亚群;已知的2019-nCoV与SARS冠状病毒的5’非翻译区条形码完全一样。作为本研究的最大贡献,我们在国际上首次提出5’非翻译区条形码可应用于病毒的检测、鉴定、分类以及进化研究。这种方法对于冠状病毒的预警和防控至关重要。本研究的最重要发现是内部核糖体进入位点很可能是影响冠状病毒毒力的重要因素。这个发现从分子水平揭示了2019-nCoV的毒力,并且为药物、抗体和疫苗的开发等应用提供直接指导。同时,我们提出一个基础理论方面的假说,起始密码子上游临近的茎环结构在真核生物的蛋白质翻译中起到重要作用。"Novel coronavirus 2019"(which was renamed subsequently"severe acute respiratory syndrome coronavirus"(SARS-CoV-2)on 11 February 2020)caused a pneumonia outbreak in Wuhan(Hubei Province,China) in December 2019. In our previous studies,two important findings regarding SARS-CoV-2 were reported,for the first time,on 21 January 2020:(1)multiple alternative translations of a coding sequence in genomes of betacoronavirus subgroup B;(2)a novel mutation in the spike(S)proteins of betacoronavirus. By this mutation,SARS-CoV-2 acquired a cleavage site for the furin enzyme in its S protein,which is not present in the S proteins of most other betacoronaviruses(e. g. SARS-CoV). In the present study,we performed analyses of 5’ untranslated regions(UTRs) in betacoronavirus. Using 5’ UTR barcodes, 1,265 betacoronaviruses were clustered into four classes,and viruses in each class had similar virulence. The class 1,2,3 and 4 match the subgroup C,B,A and D of betacoronavirus,respectively. In particular,SARS-CoV-2 and SARS-CoV have the same 5’ UTR barcode. As the main contribution of the present study,we developed 5’UTR barcoding to be used in the detection,identification,classification and phylogenetic analysis of,but not limited to coronavirus. Our method is very useful for early-warning,prevention and control of coronavirus. We found that internal ribosome entry sites(IRESs)may have important roles in the virulence of betacoronavirus.This important finding is reported,for the first time,to understand the virulence of SARS-CoV-2 at the molecular level. This finding can be used directly for vaccine development and design of drugs against SARSCoV-2,but such development is not limited to coronavirus only. In addition,we propose that the upstream hairpin structures neighboring the start codons in mRNAs have important roles in protein translation in eukaryotes.

关 键 词：冠状病毒 毒力 蛋白质翻译 内部核糖体进入位点 5’非翻译区 

分 类 号：R373.1[医药卫生—病原生物学] Q93[医药卫生—基础医学]