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丙型肝炎病毒(HCV)基因型 1b 在高变区 1(HVR1)的遗传变异性高于基因型 3。

Hepatitis C virus (HCV) genotype 1b displays higher genetic variability of hypervariable region 1 (HVR1) than genotype 3.

机构信息

Department of Immunopathology of Infectious and Parasitic Diseases, Medical University of Warsaw, Warsaw, Poland.

Department of Virology, Institute of Hematology and Transfusiology, Warsaw, Poland.

出版信息

Sci Rep. 2019 Sep 6;9(1):12846. doi: 10.1038/s41598-019-49258-y.

Abstract

Hepatitis C virus (HCV) is characterized by high genetic variability, which is manifested both at the inter-host and intra-host levels. However, its role in the clinical course of infection is less obvious. The aim of the present study was to determine the genetic variability of HCV HVR1 (hypervariable region 1) of genotype 1b and 3 in plasma of blood donors in the early seronegative stage of infection (HCV-RNA+, anti-HCV-) and in samples from chronically infected patients using next-generation sequencing. Sequencing errors were corrected, and haplotypes inferred using the ShoRAH software. Genetic diversity parameters (intra-host number of variants, number of nucleotide substitutions and diversity per site) were assessed by DNA SP and MEGA. During the early infection, the number of variants were significantly lower in subjects infected with genotype 3 than with genotype 1b (p < 0.02). Similarly, intra-host number of variants, number of nucleotide substitutions and diversity per site were lower in genotype 3 chronic infection (p < 0.0005). In addition, early infection was characterized by significantly lower HVR1 variability values (p < 0.04) when compared to chronic infection for both genotypes. It seems that the observed differences in HVR1 variability represent an inherent property of particular viral genotypes.

摘要

丙型肝炎病毒 (HCV) 的特点是遗传高度变异,这种变异在宿主间和宿主内都有体现。然而,其在感染的临床病程中的作用并不明显。本研究的目的是使用下一代测序技术,确定感染早期血清学阴性阶段(HCV-RNA+,抗-HCV-)的献血者血浆中 HCV HVR1(高变区 1)和慢性感染患者样本中基因型 1b 和 3 的遗传变异性。通过 ShoRAH 软件校正测序错误并推断单倍型。使用 DNA SP 和 MEGA 评估遗传多样性参数(宿主内变异数量、核苷酸替换数量和每个位点的多样性)。在早期感染中,感染基因型 3 的个体中变异数量明显低于感染基因型 1b 的个体(p<0.02)。同样,基因型 3 慢性感染中宿主内变异数量、核苷酸替换数量和每个位点的多样性也较低(p<0.0005)。此外,与慢性感染相比,早期感染的 HVR1 变异性值明显较低(p<0.04)。这两种基因型的 HVR1 变异性值的差异似乎代表了特定病毒基因型的固有特性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a6f6/6731259/256aaede8a0d/41598_2019_49258_Fig1_HTML.jpg

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