The site of the Media Sphera Publishers contains materials intended solely for healthcare professionals.
By closing this message, you confirm that you are a certified medical professional or a student of a medical educational institution.

Login
EN
+7 (495) 482-4118
+7 (495) 482-0604
+8 800 250-18-12
  • (toll-free number for subscriptions)
    Mon-Fri from 10 a.m. to 6 p.m.

  • © 1998-2025
+7 (495) 482-43-29
EN
All journals
Journal
Year
Year
Search result: 0

Kostyushev D.S.

Central Research Institute of Epidemiology of Rospotrebnadzor, Moscow, Russia

Zueva A.P.

Central Research Institute of Epidemiology of Rospotrebnadzor, Moscow, Russia;
M.V. Lomonosov Moscow State University, Moscow, Russia

Brezgin S.A.

Central Research Institute of Epidemiology of Rospotrebnadzor, Moscow, Russia

Lipatnikov A.D.

Central Research Institute of Epidemiology, Moscow, Russia;
D.I. Mendeleev University of Chemical Technology of Russia, Moscow, Russia

Simirskii V.N.

N.K. Koltzov Institute of Developmental Biology, Moscow, Russia

Glebe D.

Justus-Liebig University of Giessen, Institute of Medical Virology, Giessen, Germany

Volchkova E.V.

St. Petersburg State Pediatric Medical University of the Ministry of health of Russia, Saint-Petersburg, Russia

Shipulin G.A.

Federal State Budgetary Institution of Science Central Research Institute of Epidemiology, Russian Federal Consumer Rights Protection and Human Health Control Service, Moscow

Chulanov V.P.

Tsentral'nyĭ NII épidemiologii Rospotrebnadzora, Moskva

Overexpression of DNA-methyltransferases in persistency of cccDNA pool in chronic hepatitis B

Authors:

Kostyushev D.S., Zueva A.P., Brezgin S.A., Lipatnikov A.D., Simirskii V.N., Glebe D., Volchkova E.V., Shipulin G.A., Chulanov V.P.

More about the authors

Journal: Therapeutic Archive. 2017;89(11): 21‑26

DOI: 10.17116/terarkh2017891121-26

Views: 1900

Downloaded: 615

Download PDF (RU)
Contact the author
Table of contents

OVEREXPRESSION OF DNA-METHYLTRANSFERASES IN PERSISTENCY OF CCCDNA POOL IN CHRONIC HEPATITIS B
OVEREXPRESSION OF DNA-METHYLTRANSFERASES IN PERSISTENCY OF CCCDNA POOL IN CHRONIC HEPATITIS B

To cite this article:

Kostyushev DS, Zueva AP, Brezgin SA, et al. . Overexpression of DNA-methyltransferases in persistency of cccDNA pool in chronic hepatitis B. Therapeutic Archive. 2017;89(11):21‑26. (In Russ.)
https://doi.org/10.17116/terarkh2017891121-26

МСФ на ЯМ
Close metadata
Recommended articles:
Tumor infi­ltrating lymphocytes (TILs) in triple nega­tive breast cancer. Russian Journal of Archive of Pathology. 2024;(3):5-11
Pecu­liarities of local mRNA gene expression of pro- and anti-inflammatory cyto­kines in term pregnancy. Russian Bulletin of Obstetrician-Gynecologist. 2024;(3):6-13
Gono­coccal infe­ction. Level of N. gono­rrhoeae bacterial load and features of the disease’s clinical picture. Russian Journal of Clinical Dermatology and Vene­reology. 2024;(3):283-289
Inte­gration of NGS testing with conventional mole­cular gene­tic methods in onco­logy. P.A. Herzen Journal of Onco­logy. 2024;(6):84-90
Trichomoniasis. Concentration of Pathogen DNA and Its Rela­tionship with Clinical Mani­festations of the Disease. Russian Journal of Clinical Dermatology and Vene­reology. 2024;(6):656-661
Deve­lopment of a first LAMP kit for measles diagnostics. Labo­ratory Service. 2024;(4):28-35
Labo­ratory diagnostics of monkeypox: basic methods and prospects for new deve­lopments. Labo­ratory Service. 2024;(4):57-64
Neoadjuvant drug therapy and onco­logical outcomes in patients with stage I–II breast cancer. P.A. Herzen Journal of Onco­logy. 2025;(1):5-12

Aim. To define the role of DNA-methyltransferases of type 1 and type 3A in hepatitis B viral cycle. Materials and methods. Human hepatoma cells HepG2 with stable expression of 1.1-mer HBV genome were transfected with vectors encoding DNA-methyltransferase 1 (DNMT1), DNA-methyltransferase 3A (DNMT3A) or were co-transfected with these vectors. Total HBV DNA copy number, relative expression of pregenomic RNA (pgRNA), S-protein-encoding RNA (S-RNA) and cccDNA were analyzed by quantitative and semi-quantitative real-time PCR-analysis with TaqMan probes for assessment of DNMTs-mediated effects on HBV. Results. DNMT1 and DNMT3A suppress HBV transcription and replication, though to different magnitude. cccDNA pool is enlarged statistically significantly ≈2-fold (P<0.005) after transfection of DNMT3A, but is unaltered under DNMT1 treatment. Conclusion. DNMT3A regulates the size of cccDNA pool and is important for persistency of HBV infection.

Keywords:

hepatitis B virus (HBV)
chronic hepatitis B (CHB)
cccDNA
pgRNA
PCR
DNA-methyltransferases (DNMT)

Authors:

Kostyushev D.S.

Central Research Institute of Epidemiology of Rospotrebnadzor, Moscow, Russia

Zueva A.P.

Central Research Institute of Epidemiology of Rospotrebnadzor, Moscow, Russia;
M.V. Lomonosov Moscow State University, Moscow, Russia

Brezgin S.A.

Central Research Institute of Epidemiology of Rospotrebnadzor, Moscow, Russia

Lipatnikov A.D.

Central Research Institute of Epidemiology, Moscow, Russia;
D.I. Mendeleev University of Chemical Technology of Russia, Moscow, Russia

Simirskii V.N.

N.K. Koltzov Institute of Developmental Biology, Moscow, Russia

Glebe D.

Justus-Liebig University of Giessen, Institute of Medical Virology, Giessen, Germany

Volchkova E.V.

St. Petersburg State Pediatric Medical University of the Ministry of health of Russia, Saint-Petersburg, Russia

Shipulin G.A.

Federal State Budgetary Institution of Science Central Research Institute of Epidemiology, Russian Federal Consumer Rights Protection and Human Health Control Service, Moscow

Chulanov V.P.

Tsentral'nyĭ NII épidemiologii Rospotrebnadzora, Moskva

List of references:

  1. Custer B, Sullivan SD, Hazlet TK, Iloeje U, Veenstra DL, Kowdley KV. Global epidemiology of hepatitis B virus. Journal of Clinical Gastroenterology. 2004;38(10,Suppl.3):S158-168. https://doi.org/10.1097/00004836-200411003-00008
  2. State report «On the state of sanitary and epidemiological welfare of people in Russian Federation in 2013». Accessed at 28.11.2016. Available at: http://rospotrebnadzor.ru/documents/details.php?ELEMENT_ID=1984]
  3. Levrero M1, Pollicino T, Petersen J, Belloni L, Raimondo G, Dandri M. Control of cccDNA function in hepatitis B virus infection. Journal of Hepatology. 2009;51(3):581-592. https://doi.org/10.1016/j.jhep.2009.05.022
  4. Nassal M. HBV cccDNA: viral persistence reservoir and key obstacle for a cure of chronic hepatitis B. Gut. 2015;64(12):1972-1984. https://doi.org/10.1136/gutjnl-2015-309809
  5. Laras A1, Koskinas J, Dimou E, Kostamena A, Hadziyannis SJ. Intrahepatic levels and replicative activity of covalently closed circular hepatitis B virus DNA in chronically infected patients. Hepatology. 2006;44(3):694-702. https://doi.org/10.1002/hep.21299
  6. Hung-Chih Yang and Jia-Horng Kao. Persistence of hepatitis B virus covalently closed circular DNA in hepatocytes: molecular mechanisms and clinical significance. Emerging Microbes and Infections. 2014;3(9):e64. https://doi.org/10.1038/emi.2014.64
  7. Ying Chen, Johnny Sze, and Ming-Liang He. HBV cccDNA in patients’ sera as an indicator for HBV reactivation and an early signal of liver damage. World Journal of Gastroenterology. 2004;10(1):82-85. https://doi.org/10.3748/wjg.v10.i1.82
  8. Werle-Lapostolle B, Bowden S, Locarnini S, Wursthorn K, Petersen J, Lau G, Trepo C, Marcellin P, Goodman Z, Delaney WE 4th, Xiong S, Brosgart CL, Chen SS, Gibbs CS, Zoulim F. Persistence of cccDNA during the natural history of chronic hepatitis B and decline during adefovir dipivoxil therapy. Gastroenterology. 2004;126(7):1750-1758. https://doi.org/10.1053/j.gastro.2004.03.018
  9. Ganem D, Prince AM. Hepatitis B virus infection-natural history and clinical consequences. New England Journal of Medicine 2004;350:1118-1129. https://doi.org/10.1056/nejm200409163511228
  10. Philipp Tropberger, Alexandre Mercier, Margaret Robinson, Weidong Zhong, Don E Ganem, Meghan Holdorf. Mapping of histone modifications in episomal HBV cccDNA uncovers an unusual chromatin organization amenable to epigenetic manipulation. Proceedings of National Academy of Sciences. 2015;112(42): E5715-5724. https://doi.org/0.1073/pnas.1518090112
  11. Lemonica Koumbi1, and Peter Karayiannis. The Epigenetic Control of Hepatitis B Virus Modulates the Outcome of Infection. Frontiers in Microbiology. 2015;6:1491. https://doi.org/10.3389/fmicb.2015.01491
  12. Yi Tian, Weibing Yang, Jianxun Song, Yuzhang Wu, and Bing Ni. Hepatitis B Virus X Protein-Induced Aberrant Epigenetic Modifications Contributing to Human Hepatocellular Carcinoma Pathogenesis. Molecular Cell Biology. 2013;33(15):2810-2816. https://doi.org/10.1128/MCB.00205-13
  13. Perumal Vivekanandan, Hubert Darius-J Daniel, Rajesh Kannangai, Francisco Martinez-Murillo, and Michael Torbenson. Hepatitis B Virus Replication Induces Methylation of both Host and Viral DNA. Journal of Virology. 2010;84(9):4321-4329. https://doi.org/10.1128/JVI.02280-09
  14. Zhang Y, Mao R, Yan R, Cai D, Zhang Y, Zhu H, Kang Y, Liu H, Wang J, Qin Y, Huang Y, Guo H, Zhang J. Transcription of hepatitis B virus covalently closed circular DNA is regulated by CpG methylation during chronic infection. PLoS One. 2014;9(10): e110442. https://doi.org/10.1371/journal.pone.0110442
  15. Surbhi Jain, Ting-Tsung Chang, Sitong Chen, Batbold Boldbaatar, Adam Clemens, Selena Y. Lin, Ran Yan, Chi-Tan Hu, Haitao Guo, Timothy M. Block, Wei Song and Ying-Hsiu Su. Comprehensive DNA methylation analysis of hepatitis B virus genome in infected liver tissues. Scientific Reports. 2015;5(10478). https://doi.org/10.1038/srep10478
  16. Guo Y, Li Y, Mu S, Zhang J, Yan Z. Evidence that methylation of hepatitis B virus covalently closed circular DNA in liver tissues of patients with chronic hepatitis B modulates HBV replication. Journal of Medical Virology. 2009;81(7):1177-1183. https://doi.org/10.1002/jmv.21525
  17. Saito, Y., Y. Kanai, M. Sakamoto, H. Saito, H. Ishii, and S. Hirohashi. Expression of mRNA for DNA methyltransferases and methyl-CpG-binding proteins and DNA methylation status on CpG islands and pericentromeric satellite regions during human hepatocarcinogenesis. Hepatology. 2001;33:561-568 https://doi.org/10.1053/jhep.2001.22507
  18. Sakuma T, Masaki K, Abe-Chayama H, Mochida K, Yamamoto T, Chayama K. Highly multiplexed CRISPR-Cas9-nuclease and Cas9-nickase vectors for inactivation of hepatitis B virus. Genes Cells. 2016;21(11):1253-1262. https://doi.org/10.1111/gtc.12437
  19. Li H, Sheng C, Liu H, Liu G, Du X, Du J, Zhan L, Li P, Yang C, Qi L, Wang J, Yang X, Jia L, Xie J, Wang L, Hao R, Xu D, Tong Y, Zhou Y, Zhou J, Sun Y, Li Q, Qiu S, Song H. An Effective Molecular Target Site in Hepatitis B Virus S Gene for Cas9 Cleavage and Mutational Inactivation. International Journal of Biological Sciences. 2016;12(9):1104-13. https://doi.org/10.7150/ijbs.16064
  20. Lucifora J, Xia Y, Reisinger F, Zhang K, Stadler D, Cheng X, Sprinzl MF, Koppensteiner H, Makowska Z, Volz T, Remouchamps C, Chou WM, Thasler WE, Hüser N, Durantel D, Liang TJ, Münk C, Heim MH, Browning JL, Dejardin E, Dandri M, Schindler M, Heikenwalder M, Protzer U. Specific and nonhepatotoxic degradation of nuclear hepatitis B virus cccDNA. Science. 2014;343(6176):1221-1228. https://doi.org/10.1126/science.1243462
  21. Bloom K, Ely A, Mussolino C, Cathomen T, Arbuthnot P. Inactivation of hepatitis B virus replication in cultured cells and in vivo with engineered transcription activator-like effector nucleases. Molecular Therapy. 2013;21(10):1889-1897. https://doi.org/10.1038/mt.2013.170
  22. Guo Y1, Li Y, Mu S, Zhang J, Yan Z. Evidence that methylation of hepatitis B virus covalently closed circular DNA in liver tissues of patients with chronic hepatitis B modulates HBV replication. Journal of Medical Virology. 2009;81(7):1177-1183. https://doi.org/10.1002/jmv.21525
  23. Haiping Li, Fengmei Yang, Bo Gao, Zongtao Yu, Xiaobo Liu, Fei Xie, and Jicai Zhang. Hepatitis B virus infection in hepatocellular carcinoma tissues upregulates expression of DNA methyltransferases. International Journal of Clinical and Experimental Medicine. 2015;8(3):4175-4185.
  24. Hughes DJ, Marendy EM, Dickerson CA, Yetming KD, Sample CE, Sample JT. Contributions of CTCF and DNA methyltransferases DNMT1 and DNMT3B to Epstein-Barr virus restricted latency. Journal of Virology. 2012;86(2):1034-1045. https://doi.org/10.1128/JVI.05923-11

Close metadata

Contact the author
Email
Message
The publishing house "Media Sphere" does not provide treatment services, does not give recommendations on contacting medical institutions and specific specialists, on the prescription of medicines and dietary supplements.

Email Confirmation

An email was sent to test@gmail.com with a confirmation link. Follow the link from the letter to complete the registration on the site.

Email Confirmation

Contact us
If you have any questions, complaints or suggestions, please use this feedback form.
Email
Message
The publishing house "Media Sphere" does not provide treatment services, does not give recommendations on contacting medical institutions and specific specialists, on the prescription of medicines and dietary supplements.
Submit Application

You can become an author of one of our magazines, send a request and we will consider it in during the day.

Name
Phone
E-mail
Message
Login
Registration
E-mail
Password
Forgot Password?

Log in to the site using your account in one of the services

Password recovery
E-mail
Login
Register

We use cооkies to improve the performance of the site. By staying on our site, you agree to the terms of use of cооkies. To view our Privacy and Cookie Policy, please. click here.