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首页> 外文期刊>Journal of viral hepatitis. >Evolution of hepatitis C virus hypervariable region 1 in immunocompetent children born to HCV-infected mothers.
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Evolution of hepatitis C virus hypervariable region 1 in immunocompetent children born to HCV-infected mothers.

机译：HCV感染母亲所生的具有免疫能力的儿童中丙型肝炎病毒高变区1的演变。

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Hepatitis C virus (HCV) hypervariable region 1 (HVR1) is the most variable region of the viral genome and its heterogeneity reflects the virus-host interplay during chronicity. Paediatric HCV-infected patients develop liver disease with typical clinical features. Here, the evolution of HVR1 and its adjacent regions were ascertained in plasma samples of two HCV-positive children during a 5-year follow-up period. We report an almost complete conservation of the HVR1 amino acid sequence over time, with underlying nucleotide variability both within and outside HVR1, suggesting some kind of constraint on virus evolution, particularly within HVR1. Although overall d(N)/d(S) rates [rates of nonsynonymous nucleotide substitutions per nonsynonymous site (d(N)) and synonymous nucleotide substitutions per synonymous site (d(S))] were <1 in both patients, a high resolution analysis of selection pressures exerted at the codon level revealed few sites subject to selection and an absolute predominance of invariable positions within HVR1. The HVR1 amino acid sequences showed the antigenic properties expected for this region. Taken together, these data suggest peculiar evolutionary dynamics in our patients, which could be attributed to a mechanism of nucleotide invariability along with purifying selection operating on the HVR1. The lack of HVR1 variability may reflect the adaptation of the virus to a particular environment within each patient or a phenomenon of immune tolerance generated in these immunocompetent patients earlier in life.
机译：丙型肝炎病毒（HCV）高变区1（HVR1）是病毒基因组中变化最大的区域，其异质性反映了慢性期间病毒与宿主之间的相互作用。感染小儿HCV的患者会发展出具有典型临床特征的肝病。在这里，在5年的随访期内，在两名HCV阳性儿童的血浆样本中确定了HVR1及其邻近区域的进化。我们报道了随着时间的推移，HVR1氨基酸序列几乎完全保守，并且在HVR1内外都存在潜在的核苷酸变异性，这表明对病毒进化特别是在HVR1内的某种限制。尽管总体d（N）/ d（S）率[每个非同义位点（d（N））的非同义核苷酸取代率和每个同义位点（d（S））的同义核苷酸取代率]均低于1，对在密码子水平上施加的选择压力的分辨率分析表明，很少有位点受到选择，并且绝对占优势的是HVR1中的恒定位置。 HVR1氨基酸序列显示了该区域预期的抗原特性。综上所述，这些数据表明了我们患者的特殊进化动力学，这可能归因于核苷酸不变性的机制以及纯化对HVR1进行的选择。 HVR1变异性的缺乏可能反映了病毒对每个患者内部特定环境的适应性，或者反映了这些免疫能力强的患者在生命早期产生的免疫耐受现象。

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