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
2024-03-29
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 160–196Edited by Salemi M., Vandamme A.-M. 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

Supplementary material 1

PDF
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