Genomic analysis of 16 Colorado human NL63 coronaviruses identifies a new genotype, high sequence diversity in the N-terminal domain of the spike gene and evidence of recombination

Genomic analysis of 16 Colorado human NL63 coronaviruses identifies a new genotype, high sequence diversity in the N-terminal domain of the spike gene and evidence of recombination
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DOI:
10.1099/vir.0.044628-0
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发表时间:
2012-11-01
影响因子:
3.8
通讯作者:
Holmes, Kathryn V.
Holmes, Kathryn V.
中科院分区:
医学3区
文献类型:
--
作者:
Dominguez, Samuel R.;Sims, Gregory E.;Holmes, Kathryn V.

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本研究比较了从美国科罗拉多州呼吸道疾病患儿的呼吸道标本中分离的16株人类冠状病毒(HCoV)的全基因组序列,并描述了3年来流行的NL63病毒的流行病学和临床特征。2009年1月1日至2011年12月31日,9380份呼吸道样本中,经聚合酶链式反应检测出92份NL63 RNA呈阳性,总患病率为1%。NL63病毒在3年间均有流行,但流行和高发月份有较大的年际变化。对16株科罗拉多州NL63病毒的基因组序列与典型的HCoV-NL63病毒和其他3株来自荷兰的NL63病毒的基因组序列进行了系统发育分析,发现2005-2010年科罗拉多州存在A、B和C三种基因型,并发现了病毒株之间重组的证据。2005年、2009年和2010年,B型和C型在科罗拉多州共同传播,但A型直到2005年才传播,当时它是NL63的主要毒株。基因C代表了一种以前没有描述过的新谱系。NL63病毒基因组变异最大的是S蛋白基因的N端结构域(NTD)(nt1-600,aa1-200)。在这些NL63毒株的S蛋白的NTD中发现了10个不同的氨基酸序列,并从世界各地不同时间发现的75个NTDS部分序列中发现了不同的氨基酸序列。
This study compared the complete genome sequences of 16 NL63 strain human coronaviruses (hCoVs) from respiratory specimens of paediatric patients with respiratory disease in Colorado, USA, and characterized the epidemiology and clinical characteristics associated with circulating NL63 viruses over a 3-year period. From 1 January 2009 to 31 December 2011, 92 of 9380 respiratory specimens were found to be positive for NL63 RNA by PCR, an overall prevalence of 1 %. NL63 viruses were circulating during all 3 years, but there was considerable yearly variation in prevalence and the month of peak incidence. Phylogenetic analysis comparing the genome sequences of the 16 Colorado NL63 viruses with those of the prototypical hCoV-NL63 and three other NL63 viruses from the Netherlands demonstrated that there were three genotypes (A, B and C) circulating in Colorado from 2005 to 2010, and evidence of recombination between virus strains was found. Genotypes B and C co-circulated in Colorado in 2005, 2009 and 2010, but genotype A circulated only in 2005 when it was the predominant NL63 strain. Genotype C represents a new lineage that has not been described previously. The greatest variability in the NL63 virus genomes was found in the N-terminal domain (NTD) of the spike gene (nt 1-600, aa 1-200). Ten different amino acid sequences were found in the NTD of the spike protein among these NL63 strains and the 75 partial published sequences of NTDs from strains found at different times throughout the world.