Molecular evolution and circulation patterns of human respiratory syncytial virus subgroup A: Positively selected sites in the attachment G glycoprotein

Molecular evolution and circulation patterns of human respiratory syncytial virus subgroup A: Positively selected sites in the attachment G glycoprotein
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DOI:
10.1128/jvi.78.9.4675-4683.2004
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发表时间:
2004-05-01
影响因子:
5.4
通讯作者:
Van Ranst, M
Van Ranst, M
中科院分区:
医学2区
文献类型:
--
作者:
Zlateva, KT;Lerney, P;Van Ranst, M

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人呼吸道合胞病毒(HRSV)是婴幼儿急性下呼吸道疾病最常见的病原体,可导致终生反复感染。在这项研究中,我们分析了核苷酸序列,包括629 bp的羧基末端的HRSV A亚组菌株分离超过47年,包括112比利时菌株分离超过19年(1984年至2002年)的G糖蛋白基因。通过使用最大似然法,我们已经测试了多样化选择的存在,并确定了13个积极选择的网站,后验概率高于0.5。阳性选择下的位点对应于0糖基化位点或先前描述为单克隆抗体诱导的体外逃逸突变体的氨基酸。我们的研究结果表明,亚组A HRSV G糖蛋白的进化是由免疫压力在某些密码子的位置主要位于第二高变区的胞外域操作。系统发育分析显示,比利时人口和其他三个血统的可能灭绝的两个亚组A血统之间的长期共循环。HRSV亚群A分离株的进化速率估计为1.83 × 10 ~(-3)个核苷酸替换/位点/年,推测最近的共同祖先可追溯到20世纪40年代初。
Human respiratory syncytial virus (HRSV) is the most common etiological agent of acute lower respiratory tract disease in infants and can cause repeated infections throughout life. In this study, we have analyzed nucleotide sequences encompassing 629 bp at the carboxy terminus of the G glycoprotein gene for HRSV subgroup A strains isolated over 47 years, including 112 Belgian strains isolated over 19 consecutive years (1984 to 2002). By using a maximum likelihood method, we have tested the presence of diversifying selection and identified 13 positively selected sites with a posterior probability above 0.5. The sites under positive selection correspond to sites of 0 glycosylation or to amino acids that were previously described as monoclonal antibody-induced in vitro escape mutants. Our findings suggest that the evolution of subgroup A HRSV G glycoprotein is driven by immune pressure operating in certain codon positions located mainly in the second hypervariable region of the ectodomain. Phylogenetic analysis revealed the prolonged cocirculation of two subgroup A lineages among the Belgian population and the possible extinction of three other lineages. The evolutionary rate of HRSV subgroup A isolates was estimated to be 1.83 X 10(-3) nucleotide substitutions/site/year, projecting the most recent common ancestor back to the early 1940s.