Evidence of recombination and genetic diversity in human rhinoviruses in children with acute respiratory infection.

Evidence of recombination and genetic diversity in human rhinoviruses in children with acute respiratory infection.
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DOI:
10.1371/journal.pone.0006355
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发表时间:
2009-07-27
期刊:
影响因子:
3.7
通讯作者:
Deubel V
Deubel V
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Huang T;Wang W;Bessaud M;Ren P;Sheng J;Yan H;Zhang J;Lin X;Wang Y;Delpeyroux F;Deubel V

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人鼻病毒(hrv)是儿童急性呼吸道感染的一个非常普遍的原因。它们至少分为HRV-A、HRV-B和HRV-C三种,其特征是对基因组的5 '非翻译区(UTR)或VP4/VP2区域进行测序。鉴于对新型HRV菌株鉴定的兴趣日益增加及其在世界范围内的分布,我们在上海一家地区医院对急性呼吸道感染儿童进行了为期2年的临床和分子诊断。我们克隆并测序了一个924 nt的片段,该片段覆盖了部分5'UTR和VP4/VP2衣壳基因。827例急性下呼吸道感染患儿中64例为hrv感染。两个样本同时感染HRV-A和HRV-B或HRV-C。通过对66个hrv的VP4/VP2序列的比较分析,我们发现HRV-A和HRV-B种的菌株具有很高的多样性,其中属于新鉴定的HRV-C种的菌株的患病率为51.5%。在分析5 ' UTR片段时,我们确定了HRV-C的至少两个亚种:HRV-Cc和HRV-Ca,前者与HRV-A和HRV-B聚集不同,后者是先前在该区域与HRV-A相关序列重组的结果。获得HRV-Ca和HRV-Cc亚种各1株的全长序列进行比较分析。我们证实了它们结构蛋白的密切关系,但在HRV-Ca菌株的2A基因和3'UTR中发现了明显的额外重组事件。在33.3%的hrv感染患者中诊断出HRV-C和呼吸道合胞病毒和/或bocavavirus双重或三重感染,但未观察到与临床结果严重程度的相关性。我们的研究表明,引起儿童支气管炎和肺炎的HRV毒株具有高度的多样性。HRV-C比HRV-A和HRV-B具有优势,并鉴定出HRV-C的两个亚种,其多样性可能与原HRV-A毒株的重组有关。没有一种HRV-C毒株比HRV-A或HRV-B毒株对呼吸道损害有更高的临床影响。
Human rhinoviruses (HRVs) are a highly prevalent cause of acute respiratory infection in children. They are classified into at least three species, HRV-A, HRV-B and HRV-C, which are characterized by sequencing the 5′ untranslated region (UTR) or the VP4/VP2 region of the genome. Given the increased interest for novel HRV strain identification and their worldwide distribution, we have carried out clinical and molecular diagnosis of HRV strains in a 2-year study of children with acute respiratory infection visiting one district hospital in Shanghai. We cloned and sequenced a 924-nt fragment that covered part of the 5′UTR and the VP4/VP2 capsid genes. Sixty-four HRV-infected outpatients were diagnosed amongst 827 children with acute low respiratory tract infection. Two samples were co-infected with HRV-A and HRV-B or HRV-C. By comparative analysis of the VP4/VP2 sequences of the 66 HRVs, we showed a high diversity of strains in HRV-A and HRV-B species, and a prevalence of 51.5% of strains that belonged to the recently identified HRV-C species. When analyzing a fragment of the 5′ UTR, we characterized at least two subspecies of HRV-C: HRV-Cc, which clustered differently from HRV-A and HRV-B, and HRV-Ca, which resulted from previous recombination in this region with sequences related to HRV-A. The full-length sequence of one strain of each HRV-Ca and HRV-Cc subspecies was obtained for comparative analysis. We confirmed the close relationship of their structural proteins but showed apparent additional recombination events in the 2A gene and 3′UTR of the HRV-Ca strain. Double or triple infections with HRV-C and respiratory syncytial virus and/or bocavirus were diagnosed in 33.3% of the HRV-infected patients, but no correlation with severity of clinical outcome was observed. Our study showed a high diversity of HRV strains that cause bronchitis and pneumonia in children. A predominance of HRV-C over HRV-A and HRV-B was observed, and two subspecies of HRV-C were identified, the diversity of which seemed to be related to recombination with former HRV-A strains. None of the HRV-C strains appeared to have a higher clinical impact than HRV-A or HRV-B on respiratory compromise.
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