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Development of novel therapeutics for chronic hepatitis B

  • Published:
Virologica Sinica

Abstract

Chronic infection of hepatitis B virus (HBV) presents one of the serious public health challenges worldwide. Current treatment of chronic hepatitis B (CHB) is limited, and is composed of interferon and nucleoside/nucleotide reverse transcriptase inhibitors (NRTI). Interferon is poorly tolerated and is only responsive in a small fraction of CHB patients and NRTIs often face the problem of emergence of drug resistance during long-term treatment. The current treatment of CHB can be improved in several ways including genotyping mutations associated with drug resistance before treatment to guide the choice of NRTIs and suitable combinations among NRTIs and interferon. It is important to continue research in the identification of novel therapeutic targets in the life cycle of HBV or in the host immune system to stimulate the development of new antiviral agents and immunotherapies. Several antiviral agents targeting HBV entry, cccDNA, capsid formation, viral morphogenesis and virion secretion, as well as two therapeutic vaccines are currently being evaluated in preclinical studies or in clinical trials to assess their anti-HBV efficacy.

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References

  1. Block T M, Lu X, Mehta A S, et al. 1998. Treatment of chronic hepadnavirus infection in a woodchuck animal model with an inhibitor of protein folding and trafficking. Nat Med, 4:610–614.

    Article  CAS  PubMed  Google Scholar 

  2. Chotiyaputta W, Lok A. 2009. hepatitis B virus variants. Nat Rev Gastroenterol Hepatol, 6: 453–462.

    Article  CAS  PubMed  Google Scholar 

  3. Delaney W E 4th, Edwards R, Colledge D, et al. 2002. Phenylpropenamide derivatives AT-61 and AT-130 inhibit replication of wild-type and lamivudine-resistant strains of hepatitis B virus in vitro. Antimicrob Agents Chemother, 46: 3057–3060.

    Article  CAS  PubMed  Google Scholar 

  4. Deng Q, Zhai J W, Michel M L, et al. 2007. Identification and characterization of peptides that interact with hepatitis B virus via the putative receptor binding site. J Virol, 81: 4244–4254.

    Article  CAS  PubMed  Google Scholar 

  5. Deres K, Schroder C H, Paessens A, et al. 2003. Inhibition of hepatitis B virus replication by drug-induced depletion of nucleocapsids. Science, 299: 893–896.

    Article  CAS  PubMed  Google Scholar 

  6. Dienstag J L. 2008. Hepatitis B virus infection. N Engl J Med, 359:1486–1500.

    Article  CAS  PubMed  Google Scholar 

  7. Ganem D, Prince A M. 2004. Hepatitis B virus infection-natural history and clinical consequences. N Engl J Med, 350:1118–1129.

    Article  CAS  PubMed  Google Scholar 

  8. Glebe D, Urban S, Knoop E V, et al. 2005. Mapping of the hepatitis B virus attachment site by use of infection-inhibiting preS1 lipopeptides and tupaia hepatocytes. Gastroenterology, 129: 234–245.

    Article  CAS  PubMed  Google Scholar 

  9. Gripon P, Cannie I, Urban S. 2005. Efficient inhibition of hepatitis B virus infection by acylated peptides derived from the large viral surface protein. J Virol, 79: 1613–1622.

    Article  CAS  PubMed  Google Scholar 

  10. King R W, Ladner S K, Miller T J, et al. 1998. Inhibition of human hepatitis B virus replication by AT-61, a phenylpropenamide derivative, alone and in combination with (−)β-L-2’,3’-dideoxy-3’-thiacytidine. Antimicrob Agents Chemother, 42: 3179–3186.

    CAS  PubMed  Google Scholar 

  11. Lampertico P. Viganò M, Manenti E, et al. 2007. Low resistance to adefovir combined with lamivudine: a 3-year study of 145 lamivudine-resistant hepatitis B patients. Gastroenterology, 133: 1445–1451.

    Article  CAS  PubMed  Google Scholar 

  12. Lazar C, Durantel D, Macovei A, et al. 2007. Treatment of hepatitis B virus-infected cells with alpha-glucosidase inhibitors results in production of virions with altered molecular composition and infectivity. Antiviral Res, 76: 30–37.

    Article  CAS  PubMed  Google Scholar 

  13. Lucifora J, Durantel D, Testoni B, et al. 2010. Control of hepatitis B virus replication by innate response of HepaRG cells. Hepatology, 51: 63–72.

    CAS  PubMed  Google Scholar 

  14. Mancini-Bourgine M, Fontaine H, Bréchot C, et al. 2006. Immunogenicity of a hepatitis B DNA vaccine administered to chronic HBV carriers. Vaccine, 24: 4482–4489.

    Article  CAS  PubMed  Google Scholar 

  15. Mehta A, Carrouée S, Conyers B, et al. 2001. Inhibition of hepatitis B virus DNA replication by imino sugars without the inhibition of the DNA polymerase: therapeutic implications. Hepatology, 33: 1488–1495.

    Article  CAS  PubMed  Google Scholar 

  16. Perrillo R. 2009. Benefits and risks of interferon therapy for hepatitis B. Hepatology, 49: S103–111.

    Article  CAS  PubMed  Google Scholar 

  17. Petersen J, Dandri M, Mier W, et al. 2008. Prevention of hepatitis B virus infection in vivo by entry inhibitors derived from the large envelope protein. Nat Biotechnol, 26: 335–341.

    Article  CAS  PubMed  Google Scholar 

  18. Rehermann B, Nascimbeni M. Immunology of hepatitis B virus and hepatitis C virus infection. Nature Rev Immunol, 5: 215–229.

  19. Riordan S M, Skinner N, Kurtovic J, et al. 2006. Reduced expression of toll-like receptor 2 on peripheral monocytes in patients with chronic hepatitis B. Clin Vaccine Immunol, 13: 972–974.

    Article  CAS  PubMed  Google Scholar 

  20. Seeger C, Mason W S. 2005. Hepatitis B virus biology. Microbiol Mol Biol Rev, 2000, 64: 51–68.

    Article  Google Scholar 

  21. Shepard C W, Simard E P, Finelli L, et al. 2006. Hepatitis B virus infection: epidemiology and vaccination. Epidemiol Rev, 28: 112–125.

    Article  PubMed  Google Scholar 

  22. Thompson A J, Colledge D, Rodgers S, et al. 2009. Stimulation of the interleukin-1 receptor and Toll-like receptor 2 inhibits hepatitis B virus replication in hepatoma cell lines in vitro. Antivir Ther, 14: 797–808.

    Article  CAS  PubMed  Google Scholar 

  23. Vincent I E, Lucifora J, Durantel D, et al. 2009. Inhibitory effect of the combination of CpG-induced cytokines with lamivudine against hepatitis B virus replication in vitro. Antivir Ther, 14: 131–135.

    CAS  PubMed  Google Scholar 

  24. Weber O, Schlemmer K H, Hartmann E, et al. 2002. Inhibition of human hepatitis B virus (HBV) by a novel non-nucleosidic compound in a transgenic mouse model. Antiviral Res, 54: 69–78.

    Article  CAS  PubMed  Google Scholar 

  25. Xu D Z, Zhao K, Guo L M, et al. 2008. A randomized controlled phase IIb trial of antigen-antibody immunogenic complex therapeutic vaccine in chronic hepatitis B patients. PLoS One, 3: e2565.

    Article  PubMed  Google Scholar 

  26. Yao X, Zheng B, Zhou J, et al. 2007. Therapeutic effect of hepatitis B surface antigen-antibody complex is associated with cytolytic and non-cytolytic immune responses in hepatitis B patients. Vaccine, 25: 1771–1779.

    Article  CAS  PubMed  Google Scholar 

  27. Zimmerman K A, Fischer K P, Joyce M A, et al. 2008. Zinc finger proteins designed to specifically target duck hepatitis B virus covalently closed circular DNA inhibit viral transcription in tissue culture. J Virol, 82: 8013–8021.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Key Laboratory of Medical Molecular Virology, Shanghai Medical College, Fudan University, Shanghai, 200032, China

    You-hua Xie & Jian-wei Zhai

  2. Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China

    You-hua Xie, Wei Liu & Jing Liu

  3. Institute of Biochemistry and Cell Biology, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, China

    Ran Hong

Authors
  1. You-hua Xie
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  2. Ran Hong
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  3. Wei Liu
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  4. Jing Liu
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  5. Jian-wei Zhai
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Correspondence to You-hua Xie.

Additional information

Foundation items: This work was supported by “973” project (2005CB522902), Grand Science and Technology Special Project (2008ZX10002-010, 015) and Shanghai Municipal Government (8410706800).

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Xie, Yh., Hong, R., Liu, W. et al. Development of novel therapeutics for chronic hepatitis B. Virol. Sin. 25, 294–300 (2010). https://doi.org/10.1007/s12250-010-3138-9

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  • DOI: https://doi.org/10.1007/s12250-010-3138-9

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