Genetic variability of human respiratory syncytial virus A strains circulating in Ontario: a novel genotype with a 72 nucleotide G gene duplication.
Genetic variability of human respiratory syncytial virus A strains circulating in Ontario: a novel genotype with a 72 nucleotide G gene duplication.
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DOI：
10.1371/journal.pone.0032807
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Gubbay JB
中科院分区：
文献类型：
--
作者：
Eshaghi A;Duvvuri VR;Lai R;Nadarajah JT;Li A;Patel SN;Low DE;Gubbay JB
人类呼吸道合胞病毒(HRSV)是2岁以下儿童急性下呼吸道感染的主要原因，可导致终生反复感染。我们通过对G糖蛋白基因的测序和系统发育分析，研究了2010-2011年冬季安大略省流行的RSV-A的遗传变异性。在连续研究的201株RSV中，RSV-A(55.7%)比RSV-B(42.3%)更常见。59.8%和90.1%的甲型呼吸道合胞病毒感染发生在12月龄≤和5岁≤儿童。对112株RSV-A毒株的第二高变区进行系统发育分析，110株(98.2%)聚集于NA1基因内或邻近NA1基因，2株为GA5基因。11个(10%)与NA1相关的分离株在系统发育上聚在一起，成为一种新的RSV-A基因型，命名为on1，在附着(G)糖蛋白的C末端区域包含72个核苷酸重复。预测的多肽被延长了24个氨基酸，包括一个23个氨基酸的重复。利用RNA二级结构软件，推导出复制发生的可能机制。G基因上的23个氨基酸导致了7个潜在的O-糖基化位点的重复，包括270、275和283个残基上的3个O-连接糖受体。应用最大似然法进行系统发育分析，在安大略省NA1分离株中共观察到19个正向选择的位点；发现6个密码子恢复到RSV-A2原型株中观察到的先前状态。G-胞外区密码子回归的趋势可能推断对当前流行毒株的抗体亲和力降低。需要进一步的工作来记录和进一步了解这种具有72个核苷酸G基因重复的新型RSV-A基因型的出现、毒力、致病性和传播性。
Human respiratory syncytial virus (HRSV) is the main cause of acute lower respiratory infections in children under 2 years of age and causes repeated infections throughout life. We investigated the genetic variability of RSV-A circulating in Ontario during 2010–2011 winter season by sequencing and phylogenetic analysis of the G glycoprotein gene. Among the 201 consecutive RSV isolates studied, RSV-A (55.7%) was more commonly observed than RSV-B (42.3%). 59.8% and 90.1% of RSV-A infections were among children ≤12 months and ≤5 years old, respectively. On phylogenetic analysis of the second hypervariable region of the 112 RSV-A strains, 110 (98.2%) clustered within or adjacent to the NA1 genotype; two isolates were GA5 genotype. Eleven (10%) NA1-related isolates clustered together phylogenetically as a novel RSV-A genotype, named ON1, containing a 72 nucleotide duplication in the C-terminal region of the attachment (G) glycoprotein. The predicted polypeptide is lengthened by 24 amino acids and includes a23 amino acid duplication. Using RNA secondary structural software, a possible mechanism of duplication occurrence was derived. The 23 amino acid ON1 G gene duplication results in a repeat of 7 potential O-glycosylation sites including three O-linked sugar acceptors at residues 270, 275, and 283. Using Phylogenetic Analysis by Maximum Likelihood analysis, a total of 19 positively selected sites were observed among Ontario NA1 isolates; six were found to be codons which reverted to the previous state observed in the prototype RSV-A2 strain. The tendency of codon regression in the G-ectodomain may infer a decreased avidity of antibody to the current circulating strains. Further work is needed to document and further understand the emergence, virulence, pathogenicity and transmissibility of this novel RSV-A genotype with a72 nucleotide G gene duplication.
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影响因子：
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作者：
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