1887

Journal of General Virology header logo

Volume 85, Issue 11

Translation of hepatitis B virus (HBV) surface proteins from the HBV pregenome and precore RNAs in Semliki Forest virus-driven expression Free

Abstract

Hepatitis B virus (HBV) pregenome RNA (pgRNA) serves as a translation template for the HBV core (HBc) protein and viral polymerase (Pol). HBV precore RNA (pcRNA) directs the synthesis of the precore (preC) protein, a precursor of the hepatitis B e antigen (HBeAg). pgRNA and pcRNA were expressed in the Semliki Forest virus (SFV) expression system. Besides the HBc and preC proteins, there was revealed the synthesis of all three forms of HBV surface (HBs) proteins: long (LHBs), middle (MHBs) and short (SHBs), the start codons of which are located more than 1000 nt downstream of the HBc and preC start codons. Moreover, other HBV templates, such as 3′-truncated pgRNA lacking 3′ direct repeat and Pol mRNA, both carrying internally the HBs sequences, provided the synthesis of three HBs protein forms in the SFV-driven expression system. Maximal production of the HBs was provided by Pol mRNA, while HBc- and preC-producing templates showed relatively low internal translation of the HBs. These data allow the proposal of a ribosome leaky scanning model of internal translation initiation for HBs proteins. The putative functional role of such exceptional synthesis of the HBs proteins from the pgRNA and pcRNA templates in the natural HBV infection process needs further evaluation.

  • Received:
  • Accepted:
  • Published Online:
SGM
Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.80388-0
2004-11-01
2024-04-26
Loading full text...

Full text loading...

/deliver/fulltext/jgv/85/11/vir853343.html?itemId=/content/journal/jgv/10.1099/vir.0.80388-0&mimeType=html&fmt=ahah

References

  1. Antonucci T. K., Rutter W. J. 1989; Hepatitis B virus (HBV) promoters are regulated by the HBV enhancer in a tissue-specific manner. J Virol 63:579–583
     [Google Scholar]
  2. Bichko V., Pushko P., Dreilina D., Pumpen P., Gren E. 1985; Subtype ayw variant of hepatitis B virus. DNA primary structure analysis. FEBS Lett 185:208–212 [CrossRef]
     [Google Scholar]
  3. Blum H. E., Vyas G. N. 1983; Hepatitis B virus in non-hepatocytes. Lancet 2:920
     [Google Scholar]
  4. Bruss V. 1997; A short linear sequence in the pre-S domain of the large hepatitis B virus envelope protein required for virion formation. J Virol 71:9350–9357
     [Google Scholar]
  5. Bruss V., Vieluf K. 1995; Functions of the internal pre-S domain of the large surface protein in hepatitis B virus particle morphogenesis. J Virol 69:6652–6657
     [Google Scholar]
  6. Dejean A., Lugassy C., Zafrani S., Tiollais P., Brechot C. 1984; Detection of hepatitis B virus DNA in pancreas, kidney and skin of two human carriers of the virus. J Gen Virol 65:651–655 [CrossRef]
     [Google Scholar]
  7. Duclos-Vallee J. C., Capel F., Mabit H., Petit M. A. 1998; Phosphorylation of the hepatitis B virus core protein by glyceraldehyde-3-phosphate dehydrogenase protein kinase activity. J Gen Virol 79:1665–1670
     [Google Scholar]
  8. Fouillot N., Rossignol J. M. 1996; Translational stop codons in the precore sequence of hepatitis B virus pre-C RNA allow translation reinitiation at downstream AUGs. J Gen Virol 77:1123–1127 [CrossRef]
     [Google Scholar]
  9. Fouillot N., Tlouzeau S., Rossignol J. M., Jean-Jean O. 1993; Translation of the hepatitis B virus P gene by ribosomal scanning as an alternative to internal initiation. J Virol 67:4886–4895
     [Google Scholar]
  10. Heermann K. H., Goldmann U., Schwartz W., Seyffarth T., Baumgarten H., Gerlich W. H. 1984; Large surface proteins of hepatitis B virus containing the pre-s sequence. J Virol 52:396–402
     [Google Scholar]
  11. Hu M. C., Tranque P., Edelman G. M., Mauro V. P. 1999; rRNA-complementarity in the 5′ untranslated region of mRNA specifying the Gtx homeodomain protein: evidence that base-pairing to 18S rRNA affects translational efficiency. Proc Natl Acad Sci U S A 96:1339–1344 [CrossRef]
     [Google Scholar]
  12. Hwang W. L., Su T. S. 1999; The encapsidation signal of hepatitis B virus facilitates preC AUG recognition resulting in inefficient translation of the downstream genes. J Gen Virol 80:1769–1776
     [Google Scholar]
  13. Kann M., Sodeik B., Vlachou A., Gerlich W. H., Helenius A. 1999; Phosphorylation-dependent binding of hepatitis B virus core particles to the nuclear pore complex. J Cell Biol 145:45–55 [CrossRef]
     [Google Scholar]
  14. Kosovsky M. J., Huan B., Siddiqui A. 1996; Purification and properties of rat liver nuclear proteins that interact with the hepatitis B virus enhancer 1. J Biol Chem 271:21859–21869 [CrossRef]
     [Google Scholar]
  15. Kozak M. 1987; At least six nucleotides preceding the AUG initiator codon enhance translation in mammalian cells. J Mol Biol 196:947–950 [CrossRef]
     [Google Scholar]
  16. Kozak M. 1991; An analysis of vertebrate mRNA sequences: intimations of translational control. J Cell Biol 115:887–903 [CrossRef]
     [Google Scholar]
  17. Kozak M. 1999; Initiation of translation in prokaryotes and eukaryotes. Gene 234:187–208 [CrossRef]
     [Google Scholar]
  18. Kozak M. 2001; New ways of initiating translation in eukaryotes?. Mol Cell Biol 21:1899–1907 [CrossRef]
     [Google Scholar]
  19. Laemmli U. K. 1970; Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227:680–685 [CrossRef]
     [Google Scholar]
  20. Le Seyec J., Chouteau P., Cannie I., Guguen-Guillouzo C., Gripon P. 1998; Role of the pre-S2 domain of the large envelope protein in hepatitis B virus assembly and infectivity. J Virol 72:5573–5578
     [Google Scholar]
  21. Le Seyec J., Chouteau P., Cannie I., Guguen-Guillouzo C., Gripon P. 1999; Infection process of the hepatitis B virus depends on the presence of a defined sequence in the pre-S1 domain. J Virol 73:2052–2057
     [Google Scholar]
  22. Liljestrom P., Garoff H. 1991; A new generation of animal cell expression vectors based on the Semliki Forest virus replicon. Biotechnology (N Y) 9:1356–1361 [CrossRef]
     [Google Scholar]
  23. Lin C. G., Lo S. J. 1992; Evidence for involvement of a ribosomal leaky scanning mechanism in the translation of the hepatitis B virus pol gene from the viral pregenome RNA. Virology 188:342–352 [CrossRef]
     [Google Scholar]
  24. Lobbiani A., Lalatta F., Lugo F., Colucci G. 1990; Hepatitis B virus transcripts and surface antigen in human peripheral blood lymphocytes. J Med Virol 31:190–194 [CrossRef]
     [Google Scholar]
  25. Mauro V. P., Edelman G. M. 1997; rRNA-like sequences occur in diverse primary transcripts: implications for the control of gene expression. Proc Natl Acad Sci U S A 94:422–427 [CrossRef]
     [Google Scholar]
  26. Mauro V. P., Edelman G. M. 2002; The ribosome filter hypothesis. Proc Natl Acad Sci U S A 99:12031–12036 [CrossRef]
     [Google Scholar]
  27. Ou J. H., Laub O., Rutter W. J. 1986; Hepatitis B virus gene function: the precore region targets the core antigen to cellular membranes and causes the secretion of the e antigen. Proc Natl Acad Sci U S A 83:1578–1582 [CrossRef]
     [Google Scholar]
  28. Ou J. H., Bao H., Shih C., Tahara S. M. 1990; Preferred translation of human hepatitis B virus polymerase from core protein – but not from precore protein-specific transcript. J Virol 64:4578–4581
     [Google Scholar]
  29. Sachs A. B. 2000; Cell cycle-dependent translation initiation: IRES elements prevail. Cell 101:243–245 [CrossRef]
     [Google Scholar]
  30. Sjoberg E. M., Suomalainen M., Garoff H. 1994; A significantly improved Semliki Forest virus expression system based on translation enhancer segments from the viral capsid gene. Biotechnology (N Y) 12:1127–1131 [CrossRef]
     [Google Scholar]
  31. Stibbe W., Gerlich W. H. 1983; Structural relationships between minor and major proteins of hepatitis B surface antigen. J Virol 46:626–628
     [Google Scholar]
  32. Summers J., Mason W. S. 1982; Replication of the genome of a hepatitis B-like virus by reverse transcription of an RNA intermediate. Cell 29:403–415 [CrossRef]
     [Google Scholar]
  33. Tang H., McLachlan A. 2001; Transcriptional regulation of hepatitis B virus by nuclear hormone receptors is a critical determinant of viral tropism. Proc Natl Acad Sci U S A 98:1841–1846 [CrossRef]
     [Google Scholar]
  34. Vagner S., Galy B., Pyronnet S. 2001; Irresistible IRES. Attracting the translation machinery to internal ribosome entry sites. EMBO Rep 2:893–898 [CrossRef]
     [Google Scholar]
  35. Yaginuma K., Shirakata Y., Kobayashi M., Koike K. 1987; Hepatitis B virus (HBV) particles are produced in a cell culture system by transient expression of transfected HBV DNA. Proc Natl Acad Sci U S A 84:2678–2682 [CrossRef]
     [Google Scholar]
  36. Yeh C. T., Ou J. H. 1991; Phosphorylation of hepatitis B virus precore and core proteins. J Virol 65:2327–2331
     [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.80388-0
Loading
Translation of hepatitis B virus (HBV) surface proteins from the HBV pregenome and precore RNAs in Semliki Forest virus-driven expression
J. Gen. Virol. 85, 3343 (2004); https://doi.org/10.1099/vir.0.80388-0
/content/journal/jgv/10.1099/vir.0.80388-0
/content/journal/jgv/10.1099/vir.0.80388-0
Loading

Data & Media loading...

Most cited Most Cited RSS feed

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