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CLC number: R512.6

On-line Access: 2019-07-05

Received: 2018-08-30

Revision Accepted: 2019-02-27

Crosschecked: 2019-06-10

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Journal of Zhejiang University SCIENCE B 2019 Vol.20 No.8 P.637-646


DNA sequences homologous to hepatitis C virus (HCV) in the extrachromosomal circular DNA in peripheral blood mononuclear cells of HCV-negative subjects

Author(s):  Reinhard H. Dennin, Jian-Er Wo

Affiliation(s):  Formerly Department of Infectious Diseases and Microbiology, University of Lbeck, University Hospital Schleswig-Holstein, 23538 Lbeck, Germany; more

Corresponding email(s):   rh.dennin@t-online.de

Key Words:  Hepatitis C virus (HCV), 5'-Non-coding region (5'-NCR), Human genome, Extrachromosomal DNA, Circular DNA, Pattern of methylation

Reinhard H. Dennin, Jian-Er Wo. DNA sequences homologous to hepatitis C virus (HCV) in the extrachromosomal circular DNA in peripheral blood mononuclear cells of HCV-negative subjects[J]. Journal of Zhejiang University Science B, 2019, 20(8): 637-646.

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author="Reinhard H. Dennin, Jian-Er Wo",
journal="Journal of Zhejiang University Science B",
publisher="Zhejiang University Press & Springer",

%0 Journal Article
%T DNA sequences homologous to hepatitis C virus (HCV) in the extrachromosomal circular DNA in peripheral blood mononuclear cells of HCV-negative subjects
%A Reinhard H. Dennin
%A Jian-Er Wo
%J Journal of Zhejiang University SCIENCE B
%V 20
%N 8
%P 637-646
%@ 1673-1581
%D 2019
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B1800453

T1 - DNA sequences homologous to hepatitis C virus (HCV) in the extrachromosomal circular DNA in peripheral blood mononuclear cells of HCV-negative subjects
A1 - Reinhard H. Dennin
A1 - Jian-Er Wo
J0 - Journal of Zhejiang University Science B
VL - 20
IS - 8
SP - 637
EP - 646
%@ 1673-1581
Y1 - 2019
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B1800453

Objective: This study aimed to investigate DNA sequences that are substantially homologous to the corresponding RNA sequence sections of the hepatitis C virus (HCV). These DNA sequences are present in the whole DNA extracted from peripheral blood mononuclear cells (PBMCs) of HCV-negative subjects. We presumed that these experimentally proven 5'-noncoding region (5'-NCR) homologous DNA sequences could be contained in the extrachromosomal circular DNA (eccDNA) fraction as part of the whole cellular DNA. Methods: Home-made polymerase chain reaction (PCR) with whole cellular and isolated eccDNA, nucleotide basic local alignment search tool (BLASTn) alignments, and tests for patterns of methylation in selected sequence sections were performed. Results: The PCR tests revealed DNA sequences of up to 320 bp that broadly matched the corresponding sequence sections of known HCV genotypes. In contrast, BLASTn alignment searches of published HCV 5'-NCR sequences with human genome databases revealed only sequence segments of up to 36 bp of the 5'-NCR. The composition of these sequences shows missing base pairs, base pair mismatches as well as complete homology with HCV reference sequences. These short sequence sections are present in numerous copies on both the same and different chromosomes. The selected sequence region within the DNA sequences of the 5'-NCR revealed a broad diversity of individual patterns of methylation. Conclusions: The experimental results confirm our assumption that parts of the HCV 5'-NCR genomic RNA sequences are present at the DNA level in the eccDNA fraction of PBMCs. The tests for methylation patterns therein revealed individual methylomes which could represent an epigenetic feature. The respective sequence section might be subject to genetic regulation.


创新点:首次从HCV阴性者eccDNA中检测到HCV 5’-非编码区(5’-NCR)基因组RNA序列,验证了我们的假设: HCV同源DNA序列存在于人的外周血单核细胞的eccDNA组分中.
结论:实验结果证实了我们的假设:即部分HCV 5’-NCR基因组RNA序列存在于外周血单核细胞的eccDNA组分.同时,甲基化分析结果显示了个体间的甲基化模式所代表的受遗传调控的表观遗传特征.


Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article


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[41]List of electronic supplementary materials

[42]Data S1 Materials and methods, supporting online information for protocols

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