Polymerase mutations rtN238R, rtT240Y and rtN248H of hepatitis B virus decrease susceptibility to adefovir

详细信息    查看全文

• 作者：Bo Qin (15770) (25770) (35770)
  RongJuan Pei (15770)
  TingTing He (25770)
  ZhaoHui Huang (25770)
  GuoShao Pan (25770)
  ChunYu Tu (25770)
  MengJi Lu (15770) (35770)
  XinWen Chen (15770)
  
• 关键词：hepatitis B virus ; resistance mutation ; adefovir dipivoxil (ADV)
• 刊名：Chinese Science Bulletin
• 出版年：2013
• 出版时间：May 2013
• 年：2013
• 卷：58
• 期：15
• 页码：1760-1766
• 全文大小：1472KB
• 参考文献：1. Beck J, Nassal M. Hepatitis B virus replication. World J Gastroenterol, 2007, 13: 48鈥?4
  2. Gao W, Hu J. Formation of hepatitis B virus covalently closed circular DNA: Removal of genome-linked protein. J Virol, 2007, 81: 6164鈥?174 10.1128/JVI.02721-06">CrossRef
  3. Mizokami M, Orito E, Ohba K, et al. Constrained evolution with respect to gene overlap of hepatitis B virus. J Mol Evol, 1997, 44(Suppl 1): S83鈥?0 10.1007/PL00000061">CrossRef
  4. Lee W M. Hepatitis B virus infection. N Engl J Med, 1997, 337: 1733鈥?745 10.1056/NEJM199712113372406">CrossRef
  5. Behal R, Jain R, Behal K K, et al. Seroprevalence and risk factors for hepatitis B virus infection among general population in northern India. Arq Gastroenterol, 2008, 45: 137鈥?40 10.1590/S0004-28032008000200009">CrossRef
  6. Mahoney F J. Update on diagnosis, management, and prevention of hepatitis B virus infection. Clin Microbiol Rev, 1999, 12: 351鈥?66
  7. Schildgen V, Ziegler S, Tillmann R L, et al. Novel mutation in YMDD motif and direct neighbourhood in a child with chronic HBV-infection and clinical lamivudine and adefovir resistance-A scholarly case. Virol J, 2010, 7: 167 10.1186/1743-422X-7-167">CrossRef
  8. 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鈥?15 10.1016/0092-8674(82)90157-X">CrossRef
  9. Gunther S, Fischer L, Pult I, et al. Naturally occurring variants of hepatitis B virus. Adv Virus Res, 1999, 52: 25鈥?37 10.1016/S0065-3527(08)60298-5">CrossRef
  10. Yuen M F, Lai C L. Treatment of chronic hepatitis B. Lancet Infect Dis, 2001, 1: 232鈥?41 10.1016/S1473-3099(01)00118-9">CrossRef
  11. Fung J, Lai C L, Seto W K, et al. Nucleoside/nucleotide analogues in the treatment of chronic hepatitis B. J Antimicrob Chemother, 2011, 66: 2715鈥?725 10.1093/jac/dkr388">CrossRef
  12. Zoulim F, Locarnini S. Hepatitis B virus resistance to nucleos(t)ide analogues. Gastroenterology, 2009, 137: 1593鈥?608 10.1053/j.gastro.2009.08.063">CrossRef
  13. Zoulim F. Antiviral therapy of chronic hepatitis B. Antiviral Res, 2006, 71: 206鈥?15 10.1016/j.antiviral.2006.04.003">CrossRef
  14. Kwon H, Lok A S. Hepatitis B therapy. Nat Rev, 2011, 8: 275鈥?84
  15. Torresi J, Earnest-Silveira L, Civitico G, et al. Restoration of replication phenotype of lamivudine-resistant hepatitis B virus mutants by compensatory changes in the 鈥淔ingers鈥?Subdomain of the viral polymerase selected as a consequence of mutations in the overlappings gene. Virology, 2002, 299: 88鈥?9 10.1006/viro.2002.1448">CrossRef
  16. Brunelle M N, Jacquard A C, Pichoud C, et al. Susceptibility to antivirals of a human HBV strain with mutations conferring resistance to both lamivudine and adefovir. Hepatology, 2005, 41: 1391鈥?398 10.1002/hep.20723">CrossRef
  17. Pallier C, Castera L, Soulier A, et al. Dynamics of hepatitis B virus resistance to lamivudine. J Virol, 2006, 80: 643鈥?53 10.1128/JVI.80.2.643-653.2006">CrossRef
  18. Osiowy C, Villeneuve J P, Heathcote E J, et al. Detection of rtN236T and rtA181V/T mutations associated with resistance to adefovir dipivoxil in samples from patients with chronic hepatitis B virus infection by the INNO-LiPA HBV DR line probe assay (version 2). J Clin Microbiol, 2006, 44: 1994鈥?997 10.1128/JCM.02477-05">CrossRef
  19. Leung N. Viral resistance in HBV infection: Diagnosis, implications and management. Trop Gastroenterol, 2008, 29: 123鈥?28
  20. Amini Bavil Olyaee S, Herbers U, Sheldon J, et al. The rtA194T polymerase mutation impacts viral replication and susceptibility to tenofovir in hepatitis B e antigen-positive and hepatitis B e antigen-negative hepatitis B virus strains. Hepatology, 2009, 49: 1158鈥?165 10.1002/hep.22790">CrossRef
  21. Sheldon J, Camino N, Rodes B, et al. Selection of hepatitis B virus polymerase mutations in HIV-coinfected patients treated with tenofovir. Antivir Ther, 2005, 10: 727鈥?34
  22. Delaney W E, Ray A S, Yang H, et al. Intracellular metabolism and / in vitro activity of tenofovir against hepatitis B virus. Antimicrob Agents Chemother, 2006, 50: 2471鈥?477 10.1128/AAC.00138-06">CrossRef
  23. Wu C, Deng W, Deng L, et al. Amino acid substitutions at positions 122 and 145 of hepatitis B virus surface antigen (HBsAg) determine the antigenicity and immunogenicity of HBsAg and influence / in vivo HBsAg clearance. J Virol, 2012, 86: 4658鈥?669 10.1128/JVI.06353-11">CrossRef
  24. Lei Y C, Hao Y H, Zhang Z M, et al. Inhibition of hepatitis B virus replication by APOBEC3G / in vitro and / in vivo. World J Gastroenterol, 2006, 12: 4492鈥?497
  25. Qiu J, Qin B, Rayner S, et al. Novel evidence suggests hepatitis B virus surface proteins participate in regulation of HBV genome replication. Virol Sin, 2011, 26: 131鈥?38 10.1007/s12250-011-3190-0">CrossRef
  26. Kain S R. Use of secreted alkaline phosphatase as a reporter of gene expression in mammalian cells. Methods Mol Biol, 1997, 63: 49鈥?0
  27. Pan X B, Wei L, Han J C, et al. Artificial recombinant cell-penetrating peptides interfere with envelopment of hepatitis B virus nucleocapsid and viral production. Antiviral Res, 2011, 89: 109鈥?14 10.1016/j.antiviral.2010.12.001">CrossRef
  28. Guarnieri M, Kim K H, Bang G, et al. Point mutations upstream of hepatitis B virus core gene affect DNA replication at the step of core protein expression. J Virol, 2006, 80: 587鈥?95 10.1128/JVI.80.2.587-595.2006">CrossRef
  29. Meng Z, Xu Y, Wu J, et al. Inhibition of hepatitis B virus gene expression and replication by endoribonuclease-prepared siRNA. J Virol Methods, 2008, 150: 27鈥?3 10.1016/j.jviromet.2008.02.008">CrossRef
  30. Untergasser A, Zedler U, Langenkamp A, et al. Dendritic cells take up viral antigens but do not support the early steps of hepatitis B virus infection. Hepatology, 2006, 43: 539鈥?47 10.1002/hep.21048">CrossRef
  31. Santantonio T, Fasano M, Durantel S, et al. Adefovir dipivoxil resistance patterns in patients with lamivudine-resistant chronic hepatitis B. Antivir Ther, 2009, 14: 557鈥?65
  32. Margeridon Thermet S, Shulman N S, Ahmed A, et al. Ultra-deep pyrosequencing of hepatitis B virus quasispecies from nucleoside and nucleotide reverse-transcriptase inhibitor (NRTI)-treated patients and NRTI-naive patients. J Infect Dis, 2009, 199: 1275鈥?285 10.1086/597808">CrossRef
  33. Milazzo L, Corbellino M, Foschi A, et al. Late onset of hepatitis B virus reactivation following hematopoietic stem cell transplantation: Successful treatment with combined entecavir plus tenofovir therapy. Transpl Infect Dis, 2012, 14: 95鈥?8 10.1111/j.1399-3062.2011.00659.x">CrossRef
  34. Wu C, Zhang X, Tian Y, et al. Biological significance of amino acid substitutions in hepatitis B surface antigen (HBsAg) for glycosylation, secretion, antigenicity and immunogenicity of HBsAg and hepatitis B virus replication. J Gen Virol, 2010, 91: 483鈥?92 10.1099/vir.0.012740-0">CrossRef
  35. Lok A S. Hepatitis B infection: Pathogenesis and management. J Hepatol, 2000, 32: 89鈥?7 10.1016/S0168-8278(00)80418-3">CrossRef
  36. Jarvis B, Faulds D. Lamivudine. A review of its therapeutic potential in chronic hepatitis B. Drugs, 1999, 58: 101鈥?41 10.2165/00003495-199958010-00015">CrossRef
  37. Liu B M, Li T, Xu J, et al. Characterization of potential antiviral resistance mutations in hepatitis B virus reverse transcriptase sequences in treatment-naive chinese patients. Antiviral Res, 2010, 85: 512鈥?19 10.1016/j.antiviral.2009.12.006">CrossRef
  38. Tan J, Degertekin B, Wong S N, et al. Tenofovir monotherapy is effective in hepatitis B patients with antiviral treatment failure to adefovir in the absence of adefovir-resistant mutations. J Hepatol, 2008, 48: 391鈥?98 10.1016/j.jhep.2007.09.020">CrossRef
  39. Galmarini C M, Mackey J R, Dumontet C. Nucleoside analogues: Mechanisms of drug resistance and reversal strategies. Leukemia, 2001, 15: 875鈥?90 10.1038/sj.leu.2402114">CrossRef
  40. Cha C K, Kwon H C, Cheong J Y, et al. Association of lamivudine-resistant mutational patterns with the antiviral effect of adefovir in patients with chronic hepatitis B. J Med Virol, 2009, 81: 417鈥?24 10.1002/jmv.21402">CrossRef
  41. Lee Y S, Suh D J, Lim Y S, et al. Increased risk of adefovir resistance in patients with lamivudine-resistant chronic hepatitis B after 48 weeks of adefovir dipivoxil monotherapy. Hepatology, 2006, 43: 1385鈥?391 10.1002/hep.21189">CrossRef
  
• 作者单位：Bo Qin (15770) (25770) (35770)
  RongJuan Pei (15770)
  TingTing He (25770)
  ZhaoHui Huang (25770)
  GuoShao Pan (25770)
  ChunYu Tu (25770)
  MengJi Lu (15770) (35770)
  XinWen Chen (15770)
  
  15770. State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, 430071, China
  25770. Shaoxing Centre for Disease Control and Prevention, Shaoxing, 321071, China
  35770. Institute of Virology, University Hospital of Essen, Essen, 45122, Germany
  
• ISSN：1861-9541

文摘

Long term antiviral therapy with nucleos(t)ide analogs (NAs) may lead to the emergence of drug-resistance viral mutants in chronic hepatitis B virus (HBV) patient. The purpose of this study was to identify adefovir dipivoxil (ADV) resistance mutations of HBV polymerase and determine effective drugs to replace ADV. The reverse transcriptase (RT) coding region was PCR-amplified using HBV DNA extracted from patient blood samples and sequenced. Nineteen substitution mutations were detected. Among them, rtN238R, rtT240Y and rtN248H were often observed in patients receiving ADV administration. These three potential drug resistant sites were introduced into HBV replication-competent plasmids. The in vitro susceptibility of both wild-type (WT) and mutant-type (MT) HBV to NAs was analyzed by Southern blotting and quantitative real-time PCR. The rtN238R, rtT240Y and rtN248H substitutions had no obvious effect on HBV DNA replication or gene expression. The in vitro susceptibility analysis showed that rtN238R, rtT240Y and rtN248H substitutions were responsible for the reduced susceptibility to ADV, and demonstrated a 5.42-, 2.89- and 5.72-fold increase in resistance towards ADV, respectively. However, HBV harbored these mutations retained normal susceptibility to LMV, LdT, ETV and TDF.