Naturally Occurring Genetic Deletions or Insertions in Basal Core Promoter and PreS1 Region Do Not Critically Affect Hepatitis B Virus Replication

Yihan Xiao; Zongxin Li; Xiuji Cui; Yunfan Quan

doi:doi:10.11648/j.bs.20210704.15

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Naturally Occurring Genetic Deletions or Insertions in Basal Core Promoter and PreS1 Region Do Not Critically Affect Hepatitis B Virus Replication

Yihan Xiao, Zongxin Li, Xiuji Cui, Yunfan Quan

Published in Biomedical Sciences (Volume 7, Issue 4)

Received: 11 December 2021 Accepted: 23 December 2021 Published: 29 December 2021

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Abstract

Objective: Naturally occurring genetic deletions and insertions in basal core promoter (BCP) and PreS1 region of hepatitis B virus (HBV) were frequently detected in sera of chronic hepatitis B patient and these genetic variants are related to the poor response to antiviral treatment as well as the progression of liver cirrhosis and hepatocellular carcinoma. Thus, the aim of the study was to understand the effect of genetic deletions and insertions in BCP and PreS1 region on viral replication competence. Methods: HBV DNA was extracted from the sera of a chronically HBV infected patient and the whole HBV genome was amplified by PCR method. The genome was then cloned into the pCDNA3.1 vector to construct HBV-expressing plasmid, which were used to transfect HepG2 cells. The intracellular HBV DNA was detected by Southern blot method. Results: All cloned HBV genomes carried genetic deletion or insertion in the BCP and PreS1 region. However, these mutations did not seem to affect the competence of viral replication. Conclusion: Although the genetic deletion reported here may not affect the HBV replication, patients with such genetic variation should be carefully monitored during the therapy because deletions in the BCP and PreS1 are associated with progression of liver disease.

Published in	Biomedical Sciences (Volume 7, Issue 4)
DOI	10.11648/j.bs.20210704.15
Page(s)	120-123
Creative Commons	This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.
Copyright	Copyright © The Author(s), 2024. Published by Science Publishing Group

Keywords

Basal Core Promoter, Hepatitis B Virus, PreS1, Viral Replication

References

[1]	WHO. Hepatitis B. https://www.who.int/news-room/fact-sheets/detail/hepatitis-b 2021.
[2]	Chen, B. F.; Liu, C. J.; Jow, G. M.; Chen, P. J.; Kao, J. H.; Chen, D. S. High prevalence and mapping of pre-S deletion in hepatitis B virus carriers with progressive liver diseases. Gastroenterology 2006, 130, 1153-1168, doi: 10.1053/j.gastro.2006.01.011.
[3]	Chen, C. J.; Yang, H. I.; Su, J.; Jen, C. L.; You, S. L.; Lu, S. N.; Huang, G. T.; Iloeje, U. H.; Group, R.-H. S. Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level. JAMA 2006, 295, 65-73, doi: 10.1001/jama.295.1.65.
[4]	Wang, F. S.; Fan, J. G.; Zhang, Z.; Gao, B.; Wang, H. Y. The global burden of liver disease: the major impact of China. Hepatology 2014, 60, 2099-2108, doi: 10.1002/hep.27406.
[5]	Dienstag, J. L.; Goldin, R. D.; Heathcote, E. J.; Hann, H. W.; Woessner, M.; Stephenson, S. L.; Gardner, S.; Gray, D. F.; Schiff, E. R. Histological outcome during long-term lamivudine therapy. Gastroenterology 2003, 124, 105-117, doi: 10.1053/gast.2003.50013.
[6]	Papatheodoridis, G. V.; Dimou, E.; Dimakopoulos, K.; Manolakopoulos, S.; Rapti, I.; Kitis, G.; Tzourmakliotis, D.; Manesis, E.; Hadziyannis, S. J. Outcome of hepatitis B e antigen-negative chronic hepatitis B on long-term nucleos(t)ide analog therapy starting with lamivudine. Hepatology 2005, 42, 121-129, doi: 10.1002/hep.20760.
[7]	Delius, H.; Gough, N. M.; Cameron, C. H.; Murray, K. Structure of the hepatitis B virus genome. J Virol 1983, 47, 337-343.
[8]	Hu, J.; Seeger, C. Hepadnavirus Genome Replication and Persistence. Cold Spring Harb Perspect Med 2015, 5, a021386, doi: 10.1101/cshperspect.a021386.
[9]	Summers, J.; Mason, W. S. Replication of the genome of a hepatitis B--like virus by reverse transcription of an RNA intermediate. Cell 1982, 29, 403-415.
[10]	Nassal, M. HBV cccDNA: viral persistence reservoir and key obstacle for a cure of chronic hepatitis B. Gut 2015, 64, 1972-1984, doi: 10.1136/gutjnl-2015-309809.
[11]	Bottcher, B.; Wynne, S. A.; Crowther, R. A. Determination of the fold of the core protein of hepatitis B virus by electron cryomicroscopy. Nature 1997, 386, 88-91, doi: 10.1038/386088a0.
[12]	Yaginuma, K.; Koike, K. Identification of a promoter region for 3.6-kilobase mRNA of hepatitis B virus and specific cellular binding protein. J Virol 1989, 63, 2914-2920, doi: 10.1128/JVI.63.7.2914-2920.1989.
[13]	Quarleri, J. Core promoter: a critical region where the hepatitis B virus makes decisions. World J Gastroenterol 2014, 20, 425-435, doi: 10.3748/wjg.v20.i2.425.
[14]	Cui, X. J.; Cho, Y. K.; Song, B. C. Influence of the basal core promoter and precore mutation on replication of hepatitis B virus and antiviral susceptibility of different genotypes. J Med Virol 2015, 87, 601-608, doi: 10.1002/jmv.24117.
[15]	Hunt, C. M.; McGill, J. M.; Allen, M. I.; Condreay, L. D. Clinical relevance of hepatitis B viral mutations. Hepatology 2000, 31, 1037-1044, doi: 10.1053/he.2000.6709.
[16]	Kao, J. H.; Chen, P. J.; Lai, M. Y.; Chen, D. S. Basal core promoter mutations of hepatitis B virus increase the risk of hepatocellular carcinoma in hepatitis B carriers. Gastroenterology 2003, 124, 327-334, doi: 10.1053/gast.2003.50053.
[17]	Parekh, S.; Zoulim, F.; Ahn, S. H.; Tsai, A.; Li, J.; Kawai, S.; Khan, N.; Trepo, C.; Wands, J.; Tong, S. Genome replication, virion secretion, and e antigen expression of naturally occurring hepatitis B virus core promoter mutants. J Virol 2003, 77, 6601-6612.
[18]	Lin, C. L.; Liao, L. Y.; Wang, C. S.; Chen, P. J.; Lai, M. Y.; Chen, D. S.; Kao, J. H. Basal core-promoter mutant of hepatitis B virus and progression of liver disease in hepatitis B e antigen-negative chronic hepatitis B. Liver Int 2005, 25, 564-570, doi: 10.1111/j.1478-3231.2005.01041.x.
[19]	Fu, S.; Zhang, J.; Yuan, Q.; Wang, Q.; Deng, Q.; Li, J.; Xia, N.; Wang, Y.; Wen, Y.; Tong, S. Lost Small Envelope Protein Expression from Naturally Occurring PreS1 Deletion Mutants of Hepatitis B Virus Is Often Accompanied by Increased HBx and Core Protein Expression as Well as Genome Replication. J Virol 2021, 95, e0066021, doi: 10.1128/JVI.00660-21.
[20]	Gao, W.; Hu, J. Formation of hepatitis B virus covalently closed circular DNA: removal of genome-linked protein. J Virol 2007, 81, 6164-6174, doi: 10.1128/JVI.02721-06.
[21]	Lenhoff, R. J.; Summers, J. Coordinate regulation of replication and virus assembly by the large envelope protein of an avian hepadnavirus. J Virol 1994, 68, 4565-4571, doi: 10.1128/JVI.68.7.4565-4571.1994.
[22]	Summers, J.; Smith, P. M.; Horwich, A. L. Hepadnavirus envelope proteins regulate covalently closed circular DNA amplification. J Virol 1990, 64, 2819-2824, doi: 10.1128/JVI.64.6.2819-2824.1990.
[23]	Summers, J.; Smith, P. M.; Huang, M. J.; Yu, M. S. Morphogenetic and regulatory effects of mutations in the envelope proteins of an avian hepadnavirus. J Virol 1991, 65, 1310-1317, doi: 10.1128/JVI.65.3.1310-1317.1991.
[24]	Cui, X.; Ludgate, L.; Ning, X.; Hu, J. Maturation-associated destabilization of hepatitis B virus nucleocapsid. J Virol 2013, 87, 11494-11503, doi: 10.1128/JVI.01912-13.
[25]	Torre, F.; Naoumov, N. V. Clinical implications of mutations in the hepatitis B virus genome. Eur J Clin Invest 1998, 28, 604-614.
[26]	Slagle, B. L.; Bouchard, M. J. Hepatitis B Virus X and Regulation of Viral Gene Expression. Cold Spring Harb Perspect Med 2016, 6, a021402, doi: 10.1101/cshperspect.a021402.

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APA Style

Yihan Xiao, Zongxin Li, Xiuji Cui, Yunfan Quan. (2021). Naturally Occurring Genetic Deletions or Insertions in Basal Core Promoter and PreS1 Region Do Not Critically Affect Hepatitis B Virus Replication. Biomedical Sciences, 7(4), 120-123. https://doi.org/10.11648/j.bs.20210704.15

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ACS Style

Yihan Xiao; Zongxin Li; Xiuji Cui; Yunfan Quan. Naturally Occurring Genetic Deletions or Insertions in Basal Core Promoter and PreS1 Region Do Not Critically Affect Hepatitis B Virus Replication. Biomed. Sci. 2021, 7(4), 120-123. doi: 10.11648/j.bs.20210704.15

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AMA Style

Yihan Xiao, Zongxin Li, Xiuji Cui, Yunfan Quan. Naturally Occurring Genetic Deletions or Insertions in Basal Core Promoter and PreS1 Region Do Not Critically Affect Hepatitis B Virus Replication. Biomed Sci. 2021;7(4):120-123. doi: 10.11648/j.bs.20210704.15

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@article{10.11648/j.bs.20210704.15,
  author = {Yihan Xiao and Zongxin Li and Xiuji Cui and Yunfan Quan},
  title = {Naturally Occurring Genetic Deletions or Insertions in Basal Core Promoter and PreS1 Region Do Not Critically Affect Hepatitis B Virus Replication},
  journal = {Biomedical Sciences},
  volume = {7},
  number = {4},
  pages = {120-123},
  doi = {10.11648/j.bs.20210704.15},
  url = {https://doi.org/10.11648/j.bs.20210704.15},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.bs.20210704.15},
  abstract = {Objective: Naturally occurring genetic deletions and insertions in basal core promoter (BCP) and PreS1 region of hepatitis B virus (HBV) were frequently detected in sera of chronic hepatitis B patient and these genetic variants are related to the poor response to antiviral treatment as well as the progression of liver cirrhosis and hepatocellular carcinoma. Thus, the aim of the study was to understand the effect of genetic deletions and insertions in BCP and PreS1 region on viral replication competence. Methods: HBV DNA was extracted from the sera of a chronically HBV infected patient and the whole HBV genome was amplified by PCR method. The genome was then cloned into the pCDNA3.1 vector to construct HBV-expressing plasmid, which were used to transfect HepG2 cells. The intracellular HBV DNA was detected by Southern blot method. Results: All cloned HBV genomes carried genetic deletion or insertion in the BCP and PreS1 region. However, these mutations did not seem to affect the competence of viral replication. Conclusion: Although the genetic deletion reported here may not affect the HBV replication, patients with such genetic variation should be carefully monitored during the therapy because deletions in the BCP and PreS1 are associated with progression of liver disease.},
 year = {2021}
}

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TY  - JOUR
T1  - Naturally Occurring Genetic Deletions or Insertions in Basal Core Promoter and PreS1 Region Do Not Critically Affect Hepatitis B Virus Replication
AU  - Yihan Xiao
AU  - Zongxin Li
AU  - Xiuji Cui
AU  - Yunfan Quan
Y1  - 2021/12/29
PY  - 2021
N1  - https://doi.org/10.11648/j.bs.20210704.15
DO  - 10.11648/j.bs.20210704.15
T2  - Biomedical Sciences
JF  - Biomedical Sciences
JO  - Biomedical Sciences
SP  - 120
EP  - 123
PB  - Science Publishing Group
SN  - 2575-3932
UR  - https://doi.org/10.11648/j.bs.20210704.15
AB  - Objective: Naturally occurring genetic deletions and insertions in basal core promoter (BCP) and PreS1 region of hepatitis B virus (HBV) were frequently detected in sera of chronic hepatitis B patient and these genetic variants are related to the poor response to antiviral treatment as well as the progression of liver cirrhosis and hepatocellular carcinoma. Thus, the aim of the study was to understand the effect of genetic deletions and insertions in BCP and PreS1 region on viral replication competence. Methods: HBV DNA was extracted from the sera of a chronically HBV infected patient and the whole HBV genome was amplified by PCR method. The genome was then cloned into the pCDNA3.1 vector to construct HBV-expressing plasmid, which were used to transfect HepG2 cells. The intracellular HBV DNA was detected by Southern blot method. Results: All cloned HBV genomes carried genetic deletion or insertion in the BCP and PreS1 region. However, these mutations did not seem to affect the competence of viral replication. Conclusion: Although the genetic deletion reported here may not affect the HBV replication, patients with such genetic variation should be carefully monitored during the therapy because deletions in the BCP and PreS1 are associated with progression of liver disease.
VL  - 7
IS  - 4
ER  -

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Author Information

Yihan Xiao

Key Laboratory of Tropical Translational Medicine of Ministry of Education, Hainan Medical University, Haikou, PR China
Zongxin Li

Key Laboratory of Tropical Translational Medicine of Ministry of Education, Hainan Medical University, Haikou, PR China
Xiuji Cui

Key Laboratory of Tropical Translational Medicine of Ministry of Education, Hainan Medical University, Haikou, PR China
Yunfan Quan

School of Tropical Medicine and Laboratory Medicine, Hainan Medical University, Haikou, PR China

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APA Style

Yihan Xiao, Zongxin Li, Xiuji Cui, Yunfan Quan. (2021). Naturally Occurring Genetic Deletions or Insertions in Basal Core Promoter and PreS1 Region Do Not Critically Affect Hepatitis B Virus Replication. Biomedical Sciences, 7(4), 120-123. https://doi.org/10.11648/j.bs.20210704.15

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ACS Style

Yihan Xiao; Zongxin Li; Xiuji Cui; Yunfan Quan. Naturally Occurring Genetic Deletions or Insertions in Basal Core Promoter and PreS1 Region Do Not Critically Affect Hepatitis B Virus Replication. Biomed. Sci. 2021, 7(4), 120-123. doi: 10.11648/j.bs.20210704.15

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AMA Style

Yihan Xiao, Zongxin Li, Xiuji Cui, Yunfan Quan. Naturally Occurring Genetic Deletions or Insertions in Basal Core Promoter and PreS1 Region Do Not Critically Affect Hepatitis B Virus Replication. Biomed Sci. 2021;7(4):120-123. doi: 10.11648/j.bs.20210704.15

Copy | Download

@article{10.11648/j.bs.20210704.15,
  author = {Yihan Xiao and Zongxin Li and Xiuji Cui and Yunfan Quan},
  title = {Naturally Occurring Genetic Deletions or Insertions in Basal Core Promoter and PreS1 Region Do Not Critically Affect Hepatitis B Virus Replication},
  journal = {Biomedical Sciences},
  volume = {7},
  number = {4},
  pages = {120-123},
  doi = {10.11648/j.bs.20210704.15},
  url = {https://doi.org/10.11648/j.bs.20210704.15},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.bs.20210704.15},
  abstract = {Objective: Naturally occurring genetic deletions and insertions in basal core promoter (BCP) and PreS1 region of hepatitis B virus (HBV) were frequently detected in sera of chronic hepatitis B patient and these genetic variants are related to the poor response to antiviral treatment as well as the progression of liver cirrhosis and hepatocellular carcinoma. Thus, the aim of the study was to understand the effect of genetic deletions and insertions in BCP and PreS1 region on viral replication competence. Methods: HBV DNA was extracted from the sera of a chronically HBV infected patient and the whole HBV genome was amplified by PCR method. The genome was then cloned into the pCDNA3.1 vector to construct HBV-expressing plasmid, which were used to transfect HepG2 cells. The intracellular HBV DNA was detected by Southern blot method. Results: All cloned HBV genomes carried genetic deletion or insertion in the BCP and PreS1 region. However, these mutations did not seem to affect the competence of viral replication. Conclusion: Although the genetic deletion reported here may not affect the HBV replication, patients with such genetic variation should be carefully monitored during the therapy because deletions in the BCP and PreS1 are associated with progression of liver disease.},
 year = {2021}
}

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TY  - JOUR
T1  - Naturally Occurring Genetic Deletions or Insertions in Basal Core Promoter and PreS1 Region Do Not Critically Affect Hepatitis B Virus Replication
AU  - Yihan Xiao
AU  - Zongxin Li
AU  - Xiuji Cui
AU  - Yunfan Quan
Y1  - 2021/12/29
PY  - 2021
N1  - https://doi.org/10.11648/j.bs.20210704.15
DO  - 10.11648/j.bs.20210704.15
T2  - Biomedical Sciences
JF  - Biomedical Sciences
JO  - Biomedical Sciences
SP  - 120
EP  - 123
PB  - Science Publishing Group
SN  - 2575-3932
UR  - https://doi.org/10.11648/j.bs.20210704.15
AB  - Objective: Naturally occurring genetic deletions and insertions in basal core promoter (BCP) and PreS1 region of hepatitis B virus (HBV) were frequently detected in sera of chronic hepatitis B patient and these genetic variants are related to the poor response to antiviral treatment as well as the progression of liver cirrhosis and hepatocellular carcinoma. Thus, the aim of the study was to understand the effect of genetic deletions and insertions in BCP and PreS1 region on viral replication competence. Methods: HBV DNA was extracted from the sera of a chronically HBV infected patient and the whole HBV genome was amplified by PCR method. The genome was then cloned into the pCDNA3.1 vector to construct HBV-expressing plasmid, which were used to transfect HepG2 cells. The intracellular HBV DNA was detected by Southern blot method. Results: All cloned HBV genomes carried genetic deletion or insertion in the BCP and PreS1 region. However, these mutations did not seem to affect the competence of viral replication. Conclusion: Although the genetic deletion reported here may not affect the HBV replication, patients with such genetic variation should be carefully monitored during the therapy because deletions in the BCP and PreS1 are associated with progression of liver disease.
VL  - 7
IS  - 4
ER  -

Copy | Download