Skip to main content

Advertisement

Log in

Abstract

Hepatitis B virus (HBV) is a global health problem. The HBV-mediated pathogenesis is a multistep, multi-factorial event involving crucial interplay between the chronically persisting viral factors and the host system. This triggers an immune-elicited regenerative process that eventually leads to chronic liver inflammation, scarring and formation of new tissue. Further, expression of viral antigens modulates cellular signaling, nuclear transactivation and host stress-responsive pathways that produce a cumulative effect in favor of viral survival and replication. Chronic HBV infection in India affects a sizeable population and warrants more epidemiological studies in this area. There is also an urgent need to adopt new measures to limit and manage the infection in view of our low socioeconomic status and ignorance about the disease. This review highlights the role of host and viral factors in pathogenesis and outlines their underlying mechanisms. A better understanding of the viral life cycle, mode of pathogenesis and outcome of the infection should be helpful in devising new strategies to control such wide range of HBV-associated disease and developing better interventional protocols.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. WHO fact sheet. www.who.int/mediacentre/factsheets/fs204/en/

  2. Shi YH, Shi CH (2009) Molecular characteristics and stages of chronic hepatitis B virus infection. World J Gastroenterol 15:3099–3105

    Article  PubMed  CAS  Google Scholar 

  3. Schaefer S (2007) Hepatitis B virus taxonomy and hepatitis B virus genotypes. World J Gastroenterol 13:14–21

    PubMed  CAS  Google Scholar 

  4. Chauhan R, Kazim SN, Kumar M, Bhattacharjee J, Krishnamoorthy N, Sarin SK (2008) Identification and characterization of genotype A and D recombinant hepatitis B virus from Indian chronic HBV isolates. World J Gastroenterol 28:6228–6236

    Article  Google Scholar 

  5. Chattopadhyay S, Das BC, Kar P (2008) Hepatitis B virus genotypes in chronic liver disease patients from New Delhi, India. World J Gastroenterol 12:6702–6706

    Google Scholar 

  6. Borkakoty BJ, Mahanta J, Biswas D (2008) Circulating genotypes of hepatitis B virus in Arunachal Pradesh. Indian J Med Res 127:65–70

    PubMed  CAS  Google Scholar 

  7. Arankalle VA, Gandhe SS, Borkakoty BJ, Walimbe AM, Biswas D, Mahanta J (2010) A novel HBV recombinant (genotype I) similar to Vietnam/Laos in a primitive tribe in eastern India. J Viral Hepat 17:501–510

    PubMed  CAS  Google Scholar 

  8. Datta S, Biswas A, Chandra PK, Banerjee A, Panigrahi R, Mahaoatra PK, Chakrabarti S, Panda CK, Chakravarty R (2008) Molecular epidemiology and clinical significance of hepatitis B virus genotypes, core promoter and precore mutations in eastern India. Intervirology 51:275–284

    Article  PubMed  Google Scholar 

  9. Kumar A, Kumar SI, Pandey R, Naik S, Aggarwal R (2005) Hepatitis B virus genotype A is more often associated with severe liver disease in northern India than is genotype D. Indian J Gastroenterol 24:19–22

    PubMed  CAS  Google Scholar 

  10. Thakur V, Sarin SK, Rehman S, Guptan RC, Kazim SN, Kumar S (2005) Role of HBV genotype in predicting response to lamivudine therapy in patients with chronic hepatitis B. Indian J Gastroenterol 24:12–15

    PubMed  CAS  Google Scholar 

  11. Datta S (2008) An overview of molecular epidemiology of hepatitis B virus (HBV) in India. Virol J 5:156

    Article  PubMed  Google Scholar 

  12. Madan K, Batra Y, Sreenivas V, Mizokami M, Tanaka Y, Chalamalasetty SB, Panda SK, Acharya SK (2009) HBV genotypes in India: do they influence disease severity. Hepatol Res 39:157–163

    Article  PubMed  Google Scholar 

  13. Parkin DM (2006) The global health burden of infection associated cancers in year 2002. Int J Cancer 118:3030–3044

    Article  PubMed  CAS  Google Scholar 

  14. Baumert TF, Thimme R, Weizsäcker FV (2007) Pathogenesis of hepatitis B virus infection. World J Gastroenterol 13:82–90

    PubMed  CAS  Google Scholar 

  15. Su IJ, Wang HC, Wu HC, Huang WY (2008) Ground glass hepatocytes contain pre-S mutants and represent preneoplastic lesions in chronic hepatitis B virus infection. J Gastroenterol Hepatol 23:1169–1174

    Article  PubMed  CAS  Google Scholar 

  16. Wang HC, Huang W, Lai MD, Su IJ (2006) Hepatitis B virus pre-S mutants, endoplasmic reticulum stress and hepatocarcinogenesis. Cancer Sci 97:638–683

    Article  Google Scholar 

  17. Ramesh R, Panda SK, Jameel S, Rajasambandam P (1994) Mapping of the hepatitis B virus genome in hepatocellular carcinoma using PCR and demonstration of a potential trans-activator encoded by the frequently detected fragment. J Gen Virol 75:327–334

    Article  PubMed  CAS  Google Scholar 

  18. Caselmann WH, Meyer M, Kekulé AS, Lauer U, Hofschneider PH, Koshy R (1990) A trans-activator function is generated by integration of hepatitis B virus preS/S sequences in human hepatocellular carcinoma DNA. Proc Natl Acad Sci USA 87:2970–2974

    Article  PubMed  CAS  Google Scholar 

  19. Abe K, Thung SN, Wu HC, Tran TT, Le Hoang P, Truong KD, Inui A, Jang JJ, Su IJ (2009) Pre-S2 deletion mutants of hepatitis B virus could have an important role in hepatocarcinogenesis in Asian children. Cancer Sci 100:2249–2254

    Article  PubMed  CAS  Google Scholar 

  20. Chaudhuri V, Tayal R, Nayak B, Acharya SK, Panda SK (2004) Occult hepatitis B virus infection in chronic liver disease: full-length genome and analysis of mutant surface promoter. Gastroenterology 127:1356–1371

    Article  PubMed  CAS  Google Scholar 

  21. Sengupta S, Rehman S, Durgapal H, Acharya SK, Panda SK (2007) Role of surface promoter mutations in hepatitis B surface antigen production and secretion in occult hepatitis B virus infection. J Med Virol 79:220–228

    Article  PubMed  CAS  Google Scholar 

  22. Kazim SN, Chauhan R, Das BC, Sarin SK (2006) Association of core promoter mutations with viral breakthrough in chronic hepatitis B patients on long-term lamivudine therapy. J Gastroenerol Hepatol 21:1525–1532

    Article  CAS  Google Scholar 

  23. Yeh CT (2010) Development of HBV S gene mutants in chronic hepatitis B patients receiving nucleotide/nucleoside analogue therapy. Antivir Ther 15:471–475

    Article  PubMed  CAS  Google Scholar 

  24. Sheldon J, Soriano V (2008) Hepatitis B virus escape mutants induced by antiviral therapy. J Antimicrob Chemother 61:766–768

    Article  PubMed  CAS  Google Scholar 

  25. Kazim SN, Sarin SK, Sharma BC, Khan LA, Hasnain SE (2006) Characterization of naturally occurring and lamivudine-induced surface gene mutants of hepatitis B virus in patients with chronic hepatitis B in India. Intervirology 49:152–160

    Article  PubMed  CAS  Google Scholar 

  26. Cheng P, You ZS, Kong YY, Wang Y (1999) Roles of various regions of the HBV core promoter in the transcription of Precore and pregenomic RNA. Sheng Wu Hua Xue Yu Sheng Wu Wu Li Xue Bao (Shanghai) 31:577–582

    CAS  Google Scholar 

  27. Lin CL, Liao LY, Liu CJ, Chen PJ, Lai MY, Kao JH, Chen DS (2002) Hepatitis B genotypes and precore/basal core promoter mutants in HBeAg-negative chronic hepatitis B. J Gastroenterol 37:283–287

    Article  PubMed  Google Scholar 

  28. Kidd-Ljunggren K, Oberg M, Kidd AH (1997) Hepatitis B virus X gene 1751 to 1764 mutations: implications for HBeAg status and disease. J Gen Virol 78:1469–1478

    PubMed  CAS  Google Scholar 

  29. Biswas A, Chandra PK, Datta S, Panigrahi R, Banerjee A, Chakrabarti S, Biswas K, Patra D, Bhattacharya P, Biswas K, Chakravarty R (2009) Frequency and distribution of hepatitis B virus genotypes among eastern Indian voluntary blood donors: association with precore and basal core promoter mutations. Hepatol Res 39:53–59

    Article  PubMed  CAS  Google Scholar 

  30. Kar P, Polipalli SK, Chattopadhyay S, Hssain Z, Malik A, Hsain SA, Medhi S, Begum N (2007) Prevalence of hepatitis B virus genotype D in precore mutants among chronic liver disease patients from New Delhi, India. Dig Disc Sci 52:565–569

    Article  Google Scholar 

  31. Vivekanandan P, Abraham P, Sridharan G, Chandy G, Shaji RV, Daniel D, Raghuraman S, Daniel HD, Subramaniam T (2004) High frequency of the 1896 precore mutation I patients and blood donors with hepatitis B virus infection from Indian subcontinent. Mol Diagn 8:51–56

    Article  PubMed  Google Scholar 

  32. Kramvis A, Kew MC (1999) The core promoter of hepatitis B virus. J Viral Hepat 6:415–427

    Article  PubMed  CAS  Google Scholar 

  33. Gandhe SS, Chadha MS, Walimbe AM, Arankalle VA (2003) Hepatitis B virus: prevalence of precore/core promoter mutants in different clinical categories of Indian patients. J Viral Hepat 10:367–382

    Article  PubMed  CAS  Google Scholar 

  34. Kumar A, Tiwari BK, Chaudhary AK, Pant S, Narang S (2009) Identification of a hepatitis B virus core promoter mutant by PCR-RFLP in patients suffering from chronic liver disease, Uttar Pradesh, India. Asian Pac J Cancer Prev 10:1173–1175

    PubMed  Google Scholar 

  35. Asim M, Malik A, Sarma MP, Polipalli SK, Begum N, Ahmad I, Khan LA, Husain SA, Akhtar N, Husain S, Thayumanavan L, Singla R, Kar P (2010) Hepatitis B virus BCP, Precore/core, X gene mutations/genotypes and the risk of hepatocellular carcinoma in India. J Med Virol 82:1115–1125

    Article  PubMed  CAS  Google Scholar 

  36. Chung E, Lee J, Cheong HS, Lee KY (2003) Tumor eradication by hepatitis B virus X antigen-specific CD8+ T cells in xenografted nude mice. J Immunol 170:1183–1190

    Google Scholar 

  37. Chung MK, Yoon H, Min SS, Lee HG, Kim YJ, Lee TG, Lim JS, Kim CM, Park SN (1999) Induction of cytotoxic T lymphocytes with peptides in vitro: Identification of candidate T-cell epitopes in hepatitis B virus X antigen. J Immunother 22:279–287

    Article  PubMed  CAS  Google Scholar 

  38. Hwang YK, Kim NK, Park JM, Lee K, Han WK, Kim HI, Cheong HS (2002) HLA-A2 1 restricted peptides from the HBx antigen induce specific CTL responses in vitro and in vivo. Vaccine 20:3770–3777

    Article  PubMed  CAS  Google Scholar 

  39. Malmassari S, Lone YC, Zhang M, Transy C, Michel ML (2005) In vivo hierarchy of immunodominant and subdominant HLA-A0201-restricted T-cell epitopes of HBx antigen of hepatitis B virus. Microbes Infect 7:626–634

    Article  PubMed  CAS  Google Scholar 

  40. Kumar V, Sarkar DP (2004) Hepatitis B virus X protein (HBx): structure-function relationships and role in viral pathogenesis. In: Triezenberg SJ, Kaufman J, Gossen M (eds). Handbook of Experimental Pharmacology. Springer Verlag, Heidelberg, pp 377–407

  41. Benhenda S, Cougot D, Buendia MA, Neuveut C (2009) Hepatitis B virus X protein: molecular functions and its role in viral life cycle and pathogenesis. Adv Cancer Res 103:75–109

    Article  PubMed  CAS  Google Scholar 

  42. Terradillos O, Billet O, Renard CA, Levy R, Molina T, Briand P, Buendia MA (1997) The hepatitis B virus X gene potentiates c-myc-induced liver oncogenesis in transgenic mice. Oncogene 14:395–404

    Article  PubMed  CAS  Google Scholar 

  43. Lakhtakia Kumar V, Reddi H, Mathur M, DattaGupta S, Panda SK (2003) Hepatocellular carcinoma in a hepatitis B ‘X’ transgenic mouse model: a sequential pathological evaluation. J Gastroenterol Hepatol 18:80–91

    Article  Google Scholar 

  44. Kalra N, Kumar V (2004) c-Fos is a mediator of the c-Myc-induced apoptotic signaling in serum-deprived hepatoma cells via the p38 mitogen-activated protein kinase pathway. J Biol Chem 279:25313–25319

    Article  PubMed  CAS  Google Scholar 

  45. Kim YC, Song KS, Yoon G, Nam MJ, Ryu WS (2001) Activated ras oncogene collaborates with HBx gene of hepatitis B virus to transform cells by suppressing HBx-mediated apoptosis. Oncogene 20:16–23

    Article  PubMed  CAS  Google Scholar 

  46. Oishi N, Shilagardi K, Nakamoto Y, Honda M, Kaneko S, Murakami S (2007) Hepatitis B virus X protein overcomes oncogenic RAS-induced senescence in human immortalized cells. Cancer Sci 98:1540–1548

    Article  PubMed  CAS  Google Scholar 

  47. Seok GL, Hyune MR (2000) Transcriptional repression of human p53 gene by hepatitis B virus X protein. Oncogene 19:468–471

    Article  Google Scholar 

  48. Bouchard MJ, Schneider RJ (2004) The enigmatic X gene of hepatitis B virus. J Virol 78:12725–12734

    Article  PubMed  CAS  Google Scholar 

  49. Nijhara R, Jana SS, Goswami SK, Rana AK, Majumdar SS, Kumar V, Sarkar DP (2001) Sustained activation of mitogen-activated protein kinases and AP-1 by the hepatitis B virus X protein in mouse hepatocytes in vivo. J Virol 75:10348–10358

    Article  PubMed  CAS  Google Scholar 

  50. Shirakata Y, Koike K (2003) Hepatitis B virus X protein induces cell death by causing loss of mitochondrial membrane potential. J Biol Chem 278:22071–22078

    Article  PubMed  CAS  Google Scholar 

  51. Kalra N, Kumar V (2006) The X protein of hepatitis B virus binds to the F box protein Skp2 and inhibits the ubiquitination and proteasomal degradation of c-Myc. FEBS Lett 580:431–436

    Article  PubMed  CAS  Google Scholar 

  52. Molina-J F, Benedicto I, Murata M, Martín-Vílchez S, Seki T, Antonio Pintor-Toro J, Tortolero M, Moreno-Otero R, Okazaki K, Koike K, Barbero JL, Matsuzaki K, Majano PL, López-Cabrera M (2010) Expression of pituitary tumor-transforming gene 1 (PTTG1)/securin in hepatitis B virus (HBV)-associated liver diseases: evidence for an HBV X protein-mediated inhibition of PTTG1 ubiquitination and degradation. Hepatology 51:777–787

    Article  Google Scholar 

  53. Kumar V, Jayasuryan N, Kumar R (1996) A truncated mutant (58 to 140) of the hepatitis B virus X protein (HBx) retains transactivation function. Proc Natl Acad Sci USA 93:5647–5652

    Article  PubMed  CAS  Google Scholar 

  54. Reddi H, Kumar R, Jain SK, Kumar V (2003) A carboxy-terminal region of the hepatitis B virus X protein promotes DNA interaction of CREB and mimics the native protein for transactivation function. Virus Genes 26:227–238

    Article  PubMed  CAS  Google Scholar 

  55. Park IY, Sohn BH, Yu E, Suh DJ, Chung YH, Lee JH, Surzycki SJ, Lee YI (2007) Aberrant epigenetic modifications in hepatocarcinogenesis induced by hepatitis B virus X protein. Gastroenterology 132:1476–1494

    Article  PubMed  CAS  Google Scholar 

  56. Zhao J, Wu G, Bu F, Lu B, Liang A, Cao L, Tong X, Lu X, Wu M, Guo Y (2010) Epigenetic silence of ankyrin-repeat-containing, SH3-domain-containing, and proline-rich-region- containing protein 1 (ASPP1) and ASPP2 genes promotes tumor growth in hepatitis B virus-positive hepatocellular carcinoma. Hepatology 51:142–153

    Article  PubMed  CAS  Google Scholar 

  57. Jung JK, Park SH, Jang KL (2010) Hepatitis B virus X protein overcomes the growth-inhibitory potential of retinoic acid by downregulating retinoic acid receptor-beta2 expression via DNA methylation. J Gen Virol 91:493–500

    Article  PubMed  CAS  Google Scholar 

  58. Feng Q, Stern JE, Hawes SE, Lu H, Jiang M, Kiviat NB (2010) DNA methylation changes in normal liver tissues and hepatocellular carcinoma with different viral infection. Exp Mol Pathol 88:287–292

    Article  PubMed  CAS  Google Scholar 

  59. Mukherji A, Janbandhu VC, Kumar V (2007) HBx-dependent cell cycle deregulation involves interaction with cyclin E/A-cdk2 complex and destabilization of p27Kip1. Biochem J 401:247–256

    Article  PubMed  CAS  Google Scholar 

  60. Khattar E, Kumar V (2010) Mitogenic regulation of p27Kip1 gene is mediated by AP-1 transcription factors. J Biol Chem 285:4554–4561

    Article  PubMed  CAS  Google Scholar 

  61. Mukherji A, Janbandhu VC, Kumar V (2009) HBx protein modulates PI3K/Akt pathway to overcome gentoxic stress-induced destabilization of cyclin D1 and arrest of cell cycle. Indian J Biochem Biophys 46:37–44

    PubMed  CAS  Google Scholar 

  62. Tsuge M, Hiraga N, Akiyama R, Tanaka S, Matsushita M, Mitsui F, Abe H, Kitamura S, Hatakeyama T, Kimura T, Miki D, Mori N, Imamura M, Takahashi S, Hayes CN, Chayama K (2010) HBx protein is indispensable for development of viraemia in human hepatocyte chimeric mice. J Gen Virol 91:1854–1864

    Article  PubMed  CAS  Google Scholar 

  63. Keasler VV, Hodgson AJ, Madden CR, Slagle BL (2007) Enhancement of hepatitis B virus replication by the regulatory X protein in vitro and in vivo. J Virol 81:2656–2662

    Article  PubMed  CAS  Google Scholar 

  64. Xu Z, Yen TS, Wu L, Madden CR, Tan W, Slagle BL, Ou JH (2002) Enhancement of hepatitis B virus replication by its X protein in transgenic mice. J Virol 76:2579–2584

    Article  PubMed  CAS  Google Scholar 

  65. Belloni L, Pollicino T, De Nicola F, Guerrieri F, Raffa G, Fanciulli M, Raimondo G, Levrero M (2009) Nuclear HBx binds the HBV minichromosome and modifies the epigenetic regulation of cccDNA function. Proc Natl Acad Sci USA 24:19975–19979

    Google Scholar 

  66. Gómez-Gonzalo M, Carretero M, Rullas J, Lara-Pezzi E, Aramburu J, Berkhout B, Alcamí J, López-Cabrera M (2001) The hepatitis B virus X protein induces HIV-1 replication and transcription in synergy with T-cell activation signals: functional roles of NF-kappaB/NF-AT and SP1-binding sites in the HIV-1 long terminal repeat promoter. J Biol Chem 276:35435–35443

    Article  PubMed  Google Scholar 

  67. Carretero M, Gómez-Gonzalo M, Lara-Pezzi E, Benedicto I, Aramburu J, Martínez-Martínez S, Redondo JM, López-Cabrera M (2002) The hepatitis B virus X protein binds to and activates the NH(2)-terminal trans-activation domain of nuclear factor of activated T cells-1. Virology 299:288–300

    Article  PubMed  CAS  Google Scholar 

  68. Yoo YG, Lee MO (2004) Hepatitis B virus X protein induces expression of Fas ligand gene through enhancing transcriptional activity of early growth response factor. J Biol Chem 279:36242–36249

    Article  PubMed  CAS  Google Scholar 

  69. Tang Y, Chen Y, Yang BND, Guo S, Wu Y (2009) Up-regulation of the expression of costimulatory molecule CD40 in hepatocytes by hepatitis B virus X antigen. Biochem Biophys Res Commun 384:12–17

    Article  PubMed  CAS  Google Scholar 

  70. Wu J, Meng Z, Jiang M, Pei R, Trippler M, Broering R, Bucchi A, Sowa JP, Dittmer U, Yang D, Roggendorf M, Gerken G, Lu M, Schlaak JF (2009) Hepatitis B virus suppresses toll-like receptor-mediated innate immune responses in murine parenchymal and nonparenchymal liver cells. Hepatology 49:1132–1140

    Article  PubMed  CAS  Google Scholar 

  71. Xia LM, Huang WJ, Wu JG, Yang YB, Zhang Q, Zhou ZZ, Zhu HF, Lei P, Shen GX, Tian DA (2009) HBx protein induces expression of MIG and increases migration of leukocytes through activation of NF-kappaB. Virology 385:335–342

    Article  PubMed  CAS  Google Scholar 

  72. Wei C, Ni C, Song T, Liu Y, Yang X, Zheng Z, Jia Y, Yuan Y, Guan K, Xu Y, Cheng X, Zhang Y, Yang X, Wang Y, Wen C, Wu Q, Shi W, Zhong H (2010) The hepatitis B virus X protein disrupts innate immunity by downregulating mitochondrial antiviral signaling protein. J Immunol 185:1158–1168

    Article  PubMed  CAS  Google Scholar 

  73. Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116:281–297

    Article  PubMed  CAS  Google Scholar 

  74. Skalsky RL, Cullen BR (2010) Viruses, microRNAs, and host interactions. Annu Rev Microbiol 64:123–141

    Article  PubMed  CAS  Google Scholar 

  75. Pfeffer S, Sewer A, Lagos-Quintana M, Sheridan R, Sander C, Grässer FA, van Dyk LF, Ho CK, Shuman S, Chien M, Russo JJ, Ju J, Randall G, Lindenbach BD, Rice CM, Simon V, Ho DD, Zavolan M, Tuschl T (2005) Identification of microRNAs of the herpesvirus family. Nat Methods 2:269–276

    Article  PubMed  CAS  Google Scholar 

  76. Cullen BR (2010) Five questions about viruses and microRNAs. PLoS Pathol 6:e1000787

    Article  Google Scholar 

  77. Jin WB, Wu Fl, Kong D, Guo AG (2007) HBV-encoded microRNA candidate and its target. Comput Biol Chem 31:124–126

    Article  PubMed  CAS  Google Scholar 

  78. Zhang X, Liu S, Hu T, Liu S, He Y, Sun S (2009) Up-regulated microRNA-143 transcribed by nuclear factor kappa B enhances hepatocarcinoma metastasis by repressing fibronectin expression. Hepatology 51:490–499

    Article  Google Scholar 

  79. Liu Y, Zhao J, Wang C, Li M, Han P, Wang L, Cheng Y, Fabien Z, Ma X, Xu D (2009) Altered expression profiles of microRNAs in a stable hepatitis B virus-expressing cell line. Chin Med J 122:10–14

    PubMed  CAS  Google Scholar 

  80. Yang L, Ma Z, Wang D, Zhao W, Chen L, Wang G (2010) MicroRNA-602 regulating tumor suppressive gene RASSF1A is over-expressed in hepatitis B virus-infected liver and hepatocellular carcinoma. Cancer Biol Ther 9:803–808

    PubMed  CAS  Google Scholar 

  81. Huang J, Wang Y, Guo Y, Sun S (2010) Down-regulated microRNA-152 induces aberrant DNA methylation in hepatitis B virus-related hepatocellular carcinoma by targeting DNA methyltransferase 1. Hepatology 52:60–70

    Article  PubMed  CAS  Google Scholar 

  82. Wang Y, Lu Y, Toh ST, Sung WK, Tan P, Chow P, Chung AY, Jooi LL, Lee CG (2010) Lethal-7 is down-regulated by the hepatitis B virus × protein and targets signal transducer and activator of transcription 3. J Hepatol 53:57–66

    Article  PubMed  CAS  Google Scholar 

  83. Thakur V, Kazim SN, Guptan RC, Malhotra V, Sarin SK (2003) Molecular epidemiology and transmission of hepatitis B virus in close family contacts of HBV-related chronic liver disease patients. J Med Virol 70:522-528

    Article  Google Scholar 

  84. Tandon BN, Acharya SK, Tandon A (1996) Epidemiology of hepatitis B virus infection in India. Gut 38(Suppl 2):S56–S59

    Article  PubMed  Google Scholar 

  85. Kazim SN, Wakil SM, Khan LA, Hasnain SE, Sarin SK (2002) Vertical transmission of hepatitis B virus despite maternal lamivudine therapy. Lancet 359:1488–1489

    Article  PubMed  Google Scholar 

  86. Rong Q, Zhang L, Su E, Li J, Li J, Liu Z, Huang Z, Ma W, Cao K, Huang J (2008) Bone marrow-derived mesenchymal stem cells are capable of mediating hepatitis B virus infection in injured tissues. J Viral Hepat 15:607–614

    Article  Google Scholar 

  87. Rong QF, Huang J, Su EB, Li J, Li JY, Zhang LL, Chen LL, Wang XB, Cao KJ (2008) Endothelial progenitor cell mediates transport of hepatitis B. Chin Med J 121:248–256

    PubMed  CAS  Google Scholar 

  88. Rong Q, Huang J, Su E, Li J, Li J, Zhang L, Cao K (2007) Infection of hepatitis B virus in extrahepatic endothelial tissues mediated by endothelial progenitor cells. Virol J 4:36

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Vijay Kumar.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kapoor, N.R., Kumar, V. Hepatitis B Virus: A Molecular Perspective. Proc. Natl. Acad. Sci. Sect B. Biol. Sci. 82, 31–41 (2012). https://doi.org/10.1007/s40011-011-0003-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40011-011-0003-z

Keywords

Navigation