1887

Abstract

Occult hepatitis B virus (HBV) infection (OBI), defined as the presence of HBV DNA without detectable HBV surface antigen (HBsAg), is frequent in west Africa, where genotype E is prevalent. The prevalence of OBI in 804 blood donors and 1368 pregnant women was 1.7 and 1.5 %, respectively. Nine of 32 OBI carriers were evaluated with HBV serology, viral load and complete HBV genome sequence of two to five clones. All samples except one were anti-HBV core antigen-positive and three contained antibodies against HBsAg (anti-HBs). All strains were of genotype E and formed quasispecies with 0.20–1.28 % intra-sample sequence variation. Few uncommon mutations (absent in 23 genotype E reference sequences) were found across the entire genome. Two mutations in the core region encoded truncated or abnormal capsid protein, potentially affecting viral production, but were probably rescued by non-mutated variants, as found in one clone. No evidence of escape mutants was found in anti-HBs-carrying samples, as the ‘a’ region was consistently wild type. OBI carriers constitute approximately 10 % of all HBV DNA-viraemic adult Ghanaians. OBI carriers appear as a disparate group, with a very low viral load in common, but multiple origins reflecting decades of natural evolution in an area essentially devoid of human intervention.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.83347-0
2008-02-01
2019-11-17
Loading full text...

Full text loading...

/deliver/fulltext/jgv/89/2/409.html?itemId=/content/journal/jgv/10.1099/vir.0.83347-0&mimeType=html&fmt=ahah

References

  1. Allain, J.-P. ( 2004; ). Occult hepatitis B virus infection: implications in transfusion. Vox Sang 86, 83–91.[CrossRef]
    [Google Scholar]
  2. Allain, J.-P., Candotti, D., Soldan, K., Sarkodie, F., Phelps, B., Giachetti, C., Shyamala, V., Yeboah, F., Anokwa, M. & other authors ( 2003; ). The risk of hepatitis B virus infection by transfusion in Kumasi, Ghana. Blood 101, 2419–2425.[CrossRef]
    [Google Scholar]
  3. Bock, C. T., Malek, N. P., Tillmann, H. L., Manns, M. P. & Trautwein, C. ( 2000; ). The enhancer I core region contributes to the replication level of hepatitis B virus in vivo and in vitro. J Virol 74, 2193–2202.[CrossRef]
    [Google Scholar]
  4. Brojer, E., Grabarczyk, P., Liszewski, G., Mikulska, M., Allain, J.-P. & Letowska, M. ( 2006; ). Characterization of HBV DNA positive/HBsAg negative blood donors identified in the Polish NAT screening program. Hepatology 44, 1666–1674.[CrossRef]
    [Google Scholar]
  5. Candotti, D., Opare-Sem, O., Rezvan, H., Sarkodie, F. & Allain, J.-P. ( 2006; ). Molecular and serological characterization of hepatitis B virus in deferred Ghanaian blood donors with and without elevated alanine amino transferase. J Viral Hepat 13, 715–724.[CrossRef]
    [Google Scholar]
  6. Carman, W. F., Boner, W., Fattowich, G., Colman, K., Dornan, E. S., Thursz, M. & Hadziyannis, S. ( 1997; ). Hepatitis B virus core protein mutations are concentrated in B-cell epitopes in progressive disease and in T helper cell epitopes during clinical remission. J Infect Dis 175, 1093–1100.[CrossRef]
    [Google Scholar]
  7. Chaudhuri, V., Tayal, R., Nayak, B., Acharya, S. K. & Panda, S. K. ( 2004; ). Occult hepatitis B virus infection in chronic liver disease: full-length genome analysis of mutant surface promoter. Gastroenterology 127, 1356–1371.[CrossRef]
    [Google Scholar]
  8. Chen, M., Hieng, S., Qian, X., Costa, R. & Ou, J. H. ( 1994; ). Regulation of hepatitis B virus ENI enhancer activity by hepatocyte-enriched transcription factor HNF3. Virology 205, 127–132.[CrossRef]
    [Google Scholar]
  9. Erhardt, A., Reineke, U., Blondin, D., Gerlich, W. H., Adams, O., Heintges, T., Niederau, C. & Haussinger, D. ( 2000; ). Mutations of the core promoter and response to interferon treatment in chronic replicative hepatitis B. Hepatology 31, 716–725.[CrossRef]
    [Google Scholar]
  10. Fujiwara, K., Tanaka, Y., Orito, E., Ohno, T., Kato, T., Sugihara, K., Hasegawa, I., Sakurai, M., Ito, K. & other authors ( 2005; ). Distribution of HBV genotypes among HBV carriers in Benin: phylogenetic analysis and virological characteristics of HBV genotype E. World J Gastroenterol 11, 6410–6415.
    [Google Scholar]
  11. Fukai, K., Takada, S., Yokosuka, O., Saisho, H., Omata, M. & Koike, K. ( 1997; ). Characterization of a specific region in the hepatitis B virus enhancer I for the efficient expression of X gene in the hepatic cell. Virology 236, 279–287.[CrossRef]
    [Google Scholar]
  12. Günther, S., Piwon, N., Jung, A., Iwanska, A., Schmitz, H. & Will, H. ( 2000; ). Enhanced replication contributes to enrichment of hepatitis B virus with a deletion in the core gene. Virology 273, 286–299.[CrossRef]
    [Google Scholar]
  13. Ha-Lee, Y. M., Lee, J., Pyun, H., Kim, Y., Sohn, J., Cho, Y. J. & Kim, Y. ( 2001; ). Sequence variations of hepatitis B promoter regions in persistently infected patients. Arch Virol 146, 279–292.[CrossRef]
    [Google Scholar]
  14. Hatton, T., Zhou, S. & Standring, D. N. ( 1992; ). RNA- and DNA-binding activities in hepatitis B virus capsid protein: a model for their roles in viral replication. J Virol 66, 5232–5241.
    [Google Scholar]
  15. Huy, T. T., Ishikawa, K., Ampofo, W., Izumi, T., Nakajima, A, Ansah, J., Tetteh, J. O., Nii-Trebi, N., Aidoo, S. & other authors ( 2006; ). Characteristics of hepatitis B virus in Ghana: full length genome sequences indicate the endemicity of genotype E in West Africa. J Med Virol 78, 178–184.[CrossRef]
    [Google Scholar]
  16. Jeantet, D., Chemin, I., Mandrand, B., Zoulim, F., Trepo, C. & Kay, A. ( 2002; ). Characterization of two hepatitis B virus populations isolated from a hepatitis B surface antigen-negative patient. Hepatology 35, 1215–1224.[CrossRef]
    [Google Scholar]
  17. Kramvis, A. & Kew, M. C. ( 1999; ). The core promoter of hepatitis B virus. J Viral Hepat 6, 415–427.[CrossRef]
    [Google Scholar]
  18. Kremsdorf, D., Garreau, F., Duclos, H., Thiers, V., Schellekens, H., Petit, M. A. & Brechot, C. ( 1993; ). Complete nucleotide sequence and viral envelope protein expression of a hepatitis B virus DNA derived from a hepatitis B surface antigen-seronegative patient. J Hepatol 18, 244–250.[CrossRef]
    [Google Scholar]
  19. Liao, W. & Ou, J. H. ( 1995; ). Phosphorylation and nuclear localization of the hepatitis B virus core protein: significance of serine in the three repeated SPRRR motifs. J Virol 69, 1025–1029.
    [Google Scholar]
  20. Lu, C. C. & Yen, T. S. ( 1996; ). Activation of the hepatitis B virus S promoter by transcription factor NF-Y via a CCAAT element. Virology 225, 387–394.[CrossRef]
    [Google Scholar]
  21. Mirny, L. A. & Shakhnovich, E. I. ( 1999; ). Universally conserved positions in protein folds: reading evolutionary signals about stability, folding kinetics and function. J Mol Biol 291, 177–196.[CrossRef]
    [Google Scholar]
  22. Moolla, N., Kew, M. & Arbuthnot, P. ( 2002; ). Regulatory elements of hepatitis B virus transcription. J Viral Hepat 9, 323–331.[CrossRef]
    [Google Scholar]
  23. Mulders, M. N., Venard, V., Njayou, M., Edorth, A. P., Bola Oyefolu, A. O., Kehinde, M. O., Muyembe Tamfun, J. J., Nebie, Y. K., Maiga, I. & other authors ( 2004; ). Low genetic diversity despite hyperendemicity of hepatitis B virus genotype E throughout West Africa. J Infect Dis 190, 400–408.[CrossRef]
    [Google Scholar]
  24. Nassal, M. ( 1992; ). The arginine-rich domain of the hepatitis B virus core protein is required for pregenome encapsidation and productive viral positive-strand DNA synthesis but not for virus assembly. J Virol 66, 4107–4116.
    [Google Scholar]
  25. Neurath, A. R., Kent, S. B., Strick, N. & Parker, K. ( 1986; ). Identification and chemical synthesis of a host cell receptor binding site on hepatitis B virus. Cell 46, 429–436.[CrossRef]
    [Google Scholar]
  26. Osiowy, C., Giles, E., Tanaka, Y., Mizokami, M. & Minuk, G. Y. ( 2006; ). Molecular evolution of hepatitis B virus over 25 years. J Virol 80, 10307–10314.[CrossRef]
    [Google Scholar]
  27. Owusu-Ofori, S., Temple, J., Sarkodie, F., Candotti, D. & Allain, J.-P. ( 2005; ). Predonation testing of blood donors in resource-restricted settings. Transfusion 45, 1542–1543.[CrossRef]
    [Google Scholar]
  28. Petit, M. A., Dubanchet, S., Capel, F., Voet, P., Dauguet, C. & Hauser, P. ( 1991; ). HepG2 cell binding activities of different hepatitis B virus isolates: inhibitory effect of anti-HBs and anti-preS1(21–47). Virology 180, 483–491.[CrossRef]
    [Google Scholar]
  29. Poch, O., Sauvaget, I., Delarue, M. & Tordo, N. ( 1989; ). Identification of four conserved motifs among the RNA-dependent polymerase encoding elements. EMBO J 8, 3867–3874.
    [Google Scholar]
  30. Pontisso, P., Ruvoletto, M. G., Gerlich, W. H., Heermann, K. H., Bardini, R. & Alberti, A. ( 1989; ). Identification of an attachment site for human liver plasma membranes on hepatitis B virus particles. Virology 173, 522–530.[CrossRef]
    [Google Scholar]
  31. Preisler-Adams, S., Schlayer, H. J., Peters, T., Hettler, F., Gerok, W. & Rasenack, J. ( 1993; ). Sequence analysis of hepatitis B virus DNA in immunologically negative infection. Arch Virol 133, 385–396.[CrossRef]
    [Google Scholar]
  32. Radziwill, G., Tucker, W. & Schaller, H. ( 1990; ). Mutational analysis of the hepatitis B virus P gene product: domain structure and RNase H activity. J Virol 64, 613–620.
    [Google Scholar]
  33. Raney, A. K., Le, H. B. & McLachlan, A. ( 1992; ). Regulation of transcription from the hepatitis B virus major surface antigen promoter by the Sp1 transcription factor. J Virol 66, 6912–6921.
    [Google Scholar]
  34. Rehermann, B., Ferrari, C., Pasquinelli, C. & Chisari, F. V. ( 1996; ). The hepatitis B virus persists for decades after patients' recovery from acute viral hepatitis despite active maintenance of a cytotoxic T-lymphocyte response. Nat Med 2, 1104–1108.[CrossRef]
    [Google Scholar]
  35. Roseman, A. M., Berriman, J. A., Wynne, S. A., Butler, P. J. & Crowther, R. A. ( 2005; ). A structural model for maturation of the hepatitis B virus core. Proc Natl Acad Sci U S A 102, 15821–15826.[CrossRef]
    [Google Scholar]
  36. Schories, M., Peters, T. & Rasenack, J. ( 2000; ). Isolation, characterization and biological significance of hepatitis B virus mutants from serum of a patient with immunologically negative HBV infection. J Hepatol 33, 799–811.[CrossRef]
    [Google Scholar]
  37. Shaul, Y., Ben-Levy, R. & De-Medina, T. ( 1986; ). High affinity binding site for nuclear factor I next to the hepatitis B virus S gene promoter. EMBO J 5, 1967–1971.
    [Google Scholar]
  38. Swofford, D. L. & Sullivan, J. ( 2003; ). Phylogenetic inference based on parsimony and other methods using paup*. In The Phylogenetic Handbook: A Practical Approach to DNA and Protein Phylogeny, pp. 160–196. Edited by M. Salemi & A.-M. Vandamme. Cambridge: Cambridge University Press.
  39. Uchida, T., Shimojima, S., Gotoh, K., Shikata, T. & Mima, S. ( 1994; ). Pathology of livers infected with “silent” hepatitis B virus mutant. Liver 14, 251–256.
    [Google Scholar]
  40. Uchida, T., Gotoh, K. & Shikata, T. ( 1995; ). Complete nucleotide sequences and the characteristics of two hepatitis B virus mutants causing serologically negative acute or chronic hepatitis B. J Med Virol 45, 247–252.[CrossRef]
    [Google Scholar]
  41. Weinberger, K. M., Wiedenmann, E., Bohm, S. & Jilg, W. ( 2000; ). Sensitive and accurate quantitation of hepatitis B virus DNA using kinetic fluorescence detection system (TaqMan PCR). J Virol Methods 85, 75–82.[CrossRef]
    [Google Scholar]
  42. Yotsuyanagi, H., Yasuda, K., Lino, S., Moriya, K., Shintani, Y., Fujie, H., Tsutsumi, T., Kimura, S. & Koike, K. ( 1998; ). Persistent viremia after recovery from self-limited acute hepatitis B. Hepatology 27, 1377–1382.[CrossRef]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.83347-0
Loading
/content/journal/jgv/10.1099/vir.0.83347-0
Loading

Data & Media loading...

Supplements

vol. , part 2, pp. 409 – 418

Primers used for sequencing full-length HBV amplicons [ PDF] (66 KB)



PDF

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error