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首页> 外文期刊>European review for medical and pharmacological sciences. >Analysis of hepatitis C virus core encoding sequences in chronically infected patients reveals mutability, predominance, genetic history and potential impact on therapy of Cuban genotype 1b isolates
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Analysis of hepatitis C virus core encoding sequences in chronically infected patients reveals mutability, predominance, genetic history and potential impact on therapy of Cuban genotype 1b isolates

机译：对慢性感染患者中丙型肝炎病毒核心编码序列的分析揭示了变异性，优势，遗传史以及对古巴基因型1b分离株治疗的潜在影响

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Background and Objectives: Hepatitis C virus (HCV) genotypes are relevant to epidemiological questions, vaccine development, and clinical management of chronic HCV infection. In the present work, we aimed at investigating HCV genotype, variability and genetic history of HCV isolates in Cuba from a sample of chronically infected patients. Material and Methods: A prospective study, involving 73 Cuban anti-HCV positive patients, was carried out. RT-PCR and phylogenetic analysis was employed to determine HCV genotypes. Divergence dates and demographic parameters in a Bayesian coalescent framework were estimated, as implemented in BEAST v1.4.8. Results: HCV RNA was undetectable in 15 patients that received antiviral therapy. All HCV RNA positive patients, 58, were infected with genotype 1, three of them with subtype 1a and 55 with subtype 1b. The analysis of the DNA sequence coding for a core fragment, spanning nt positions 435-816 (relative to strain H77), revealed high percent (96.7% ± 0.8%) nucleotide identity within Cuban HCV subtype 1b sequences. However, 56.7% and 20% of 30 analyzed individuals had changes in the core region in a six-month interval, at the nucleotide and amino acid level, respectively. Mutations involving aa changes were mainly found in the region encompassed between aa 70 and 106 of the core protein, with only one isolate showing a point mutation at position 43. Interestingly, some of the observed changes seem to be reversions and might in fact contribute to reducing the variability of this region. The estimated date for the most recent common ancestor of HCV genotype 1b Cuban isolates is 1969 (CI, 1953 to 1977). Discussion: Analysis of HCV core encoding sequences from chronic patients reveals mutability of genotype 1b isolates in Cuba, which seem to be predominant and rapidly multiplied during the eighty decade of last century, and might limit the benefits obtained from current antiviral therapy. Corresponding Author: Santiago Due?as-Carrer, MD; e-mail: santiago.duenas@cigb.edu.cu
机译：背景与目的：丙型肝炎病毒（HCV）基因型与流行病学问题，疫苗开发以及慢性HCV感染的临床管理有关。在目前的工作中，我们旨在调查来自慢性感染患者样本的古巴HCV分离株的HCV基因型，变异性和遗传史。材料与方法：一项前瞻性研究涉及73名古巴抗HCV阳性患者。 RT-PCR和系统发育分析被用来确定HCV基因型。如在BEAST v1.4.8中所实现的，估计了贝叶斯合并框架中的发散日期和人口统计学参数。结果：在接受抗病毒治疗的15例患者中未检测到HCV RNA。所有HCV RNA阳性患者58例均感染了基因型1，其中3例感染了1a型，55例感染了1b型。跨越核心位置435-816（相对于H77菌株）的编码核心片段的DNA序列分析显示，古巴HCV亚型1b序列具有较高的核苷酸同一性（96.7％±0.8％）。但是，在30个被分析的个体中，分别在六个月的间隔内，核苷酸和氨基酸水平的核心区域发生了变化，分别为56.7％和20％。涉及氨基酸变化的突变主要发现于核心蛋白的氨基酸70和106之间，只有一个分离物在第43位显示点突变。有趣的是，观察到的某些变化似乎是反向的，实际上可能有助于减少该区域的可变性。 HCV基因型1b古巴分离株的最近共同祖先的估计日期是1969年（CI，1953年至1977年）。讨论：对来自慢性患者的HCV核心编码序列的分析显示，古巴的1b基因型分离株具有变异性，在上个世纪八十年代似乎占主导地位并迅速繁殖，可能会限制目前抗病毒治疗的收益。通讯作者：Santiago Due？as-Carrer，医学博士;电子邮件：santiago.duenas@cigb.edu.cu

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