Genomic characterization of a newly discovered coronavirus associated with acute respiratory distress syndrome in humans.
Genomic characterization of a newly discovered coronavirus associated with acute respiratory distress syndrome in humans.
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DOI：
10.1128/mbio.00473-12
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发表时间：
2012-11-20
期刊：
影响因子：
6.4
通讯作者：
Fouchier RA
中科院分区：
文献类型：
--
作者：
van Boheemen S;de Graaf M;Lauber C;Bestebroer TM;Raj VS;Zaki AM;Osterhaus AD;Haagmans BL;Gorbalenya AE;Snijder EJ;Fouchier RA
2012年6月，一种新型人类冠状病毒（HCoV-EMC/2012）从一名患有急性肺炎和肾衰竭的男子身上分离出来。本报告描述了HCoV-EMC/2012的全基因组序列、基因组组织和表达策略及其与已知冠状病毒的关系。该基因组含有30，119个核苷酸，并含有至少10个预测的开放阅读框，其中9个被预测为从一组嵌套的7个亚基因组mRNA表达。对冠状病毒复制酶基因的系统发育分析显示，HCoV-EMC/2012与Tylonycteris bat coronavirus HKU 4（BtCoV-HKU 4）和Pipistrellus bat coronavirus HKU 5（BtCoV-HKU 5）最密切相关，这两种病毒是β冠状病毒属C谱系中的两个物种的原型。根据国际病毒分类学委员会的指导原则，并鉴于7个保守的复制酶结构域分别与BtCoV-HKU 4和BtCoV-HKU 5具有75%和77%的氨基酸序列同一性，我们建议HCoV-EMC/2012原型为β冠状病毒属中的一个新物种。HCoV-EMC/2012可能与荷兰伏翼中检测到的冠状病毒最密切相关，但由于这种蝙蝠病毒仅报告了来自基因组RNA依赖性RNA聚合酶编码区最保守部分的短序列，因此其与HCoV-EMC的遗传距离仍然不确定。HCoV-EMC/2012是已知感染人类的第六种冠状病毒，也是β冠状病毒谱系C中的第一种人类病毒。冠状病毒能够感染人类和许多动物物种。由人类冠状病毒引起的大多数感染相对温和。然而，2002年至2003年由SARS-CoV引起的严重急性呼吸综合征（SARS）的爆发和2012年由HCoV-EMC/2012引起的人类致命感染表明，冠状病毒能够在人类中引起严重的，有时是致命的疾病。我们已经确定了完整的基因组HCoV-EMC/2012使用无偏见的病毒发现方法，涉及下一代测序技术，使随后的国家最先进的生物信息学，遗传学和分类学分析。通过建立HCoV-EMC/2012的全基因组序列，将其鉴定为一个新的基因型，与SARS-CoV的蝙蝠冠状病毒有较近的亲缘关系。我们希望这些信息将是至关重要的快速推进这一新兴病原体的临床和重要的研究。
A novel human coronavirus (HCoV-EMC/2012) was isolated from a man with acute pneumonia and renal failure in June 2012. This report describes the complete genome sequence, genome organization, and expression strategy of HCoV-EMC/2012 and its relation with known coronaviruses. The genome contains 30,119 nucleotides and contains at least 10 predicted open reading frames, 9 of which are predicted to be expressed from a nested set of seven subgenomic mRNAs. Phylogenetic analysis of the replicase gene of coronaviruses with completely sequenced genomes showed that HCoV-EMC/2012 is most closely related to Tylonycteris bat coronavirus HKU4 (BtCoV-HKU4) and Pipistrellus bat coronavirus HKU5 (BtCoV-HKU5), which prototype two species in lineage C of the genus Betacoronavirus. In accordance with the guidelines of the International Committee on Taxonomy of Viruses, and in view of the 75% and 77% amino acid sequence identity in 7 conserved replicase domains with BtCoV-HKU4 and BtCoV-HKU5, respectively, we propose that HCoV-EMC/2012 prototypes a novel species in the genus Betacoronavirus. HCoV-EMC/2012 may be most closely related to a coronavirus detected in Pipistrellus pipistrellus in The Netherlands, but because only a short sequence from the most conserved part of the RNA-dependent RNA polymerase-encoding region of the genome was reported for this bat virus, its genetic distance from HCoV-EMC remains uncertain. HCoV-EMC/2012 is the sixth coronavirus known to infect humans and the first human virus within betacoronavirus lineage C. Coronaviruses are capable of infecting humans and many animal species. Most infections caused by human coronaviruses are relatively mild. However, the outbreak of severe acute respiratory syndrome (SARS) caused by SARS-CoV in 2002 to 2003 and the fatal infection of a human by HCoV-EMC/2012 in 2012 show that coronaviruses are able to cause severe, sometimes fatal disease in humans. We have determined the complete genome of HCoV-EMC/2012 using an unbiased virus discovery approach involving next-generation sequencing techniques, which enabled subsequent state-of-the-art bioinformatics, phylogenetics, and taxonomic analyses. By establishing its complete genome sequence, HCoV-EMC/2012 was characterized as a new genotype which is closely related to bat coronaviruses that are distant from SARS-CoV. We expect that this information will be vital to rapid advancement of both clinical and vital research on this emerging pathogen.