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Potential oncogene activity of the woodchuck hepatitis post-transcriptional regulatory element (WPRE)

Gene Therapy volume 12, pages 3–4 (2005)Cite this article

Sir,

Mammalian hepadnaviruses such as hepatitis B virus (HBV) and woodchuck hepatitis virus (WHV) contain a conserved post-transcriptional regulatory element (PRE) that is required for the cytoplasmic accumulation of mRNAs encoding the virion surface antigen. These PREs confer enhanced gene expression when linked with heterologous transcription units and a PRE derived from WHV (WPRE) has proven to be particularly effective.1 The WPRE has been incorporated into a number of viral vectors, including those based on retroviruses, adeno-associated viruses and lentiviruses with significant beneficial effects on transgene expression.2, 3 In our work with lentiviral vectors based on equine infectious anemia virus (EIAV), we have incorporated a WPRE into a number of vectors and demonstrated enhanced expression (unpublished data; O'Rourke et al,4 Bienemann et al).5 The WPRE element that we have used comprises nucleotides 1093–1685 (nucleotide numbering scheme of GenBank accession no. J04514) and contains the tripartite element that has been shown to be essential for enhanced gene expression. The fragment also contains an enhancer element, We1, a promoter for the WHV X protein and the sequence for the first 60 amino acids of the X protein. These sequences overlap the functional PREs. The WPRE therefore has potential promoter activity and the potential to express a 60 amino-acid X protein-derived peptide.

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References

  1. Donello JE et al. Woodchuck hepatitis virus contains a tripartite posttranscriptional regulatory element. J Vir 1998; 72: 5085–5092.

    CAS  Google Scholar 

  2. Zuffrey R et al. Woodchuck hepatitis virus posttranscriptional regulatory element enhances expression of transgenes delivered by retroviral vectors. J Vir 1999; 73: 886–892.

    Google Scholar 

  3. Loeb JE et al. Enhanced expression of transgenes from adeno-associated virus vectors with the woodchuck hepatitis virus posttranscriptional regulatory element: implications for gene therapy. Hum Gene Ther 1999; 10: 2295–2305.

    Article  CAS  Google Scholar 

  4. O'Rourke JP et al. Analysis of gene transfer and expression in skeletal muscle using enhanced EIAV lentivirus vectors. Mol Ther 2003; 7: 632–639.

    Article  CAS  Google Scholar 

  5. Bienemann AS et al. Long-term replacement of a mutated nonfunctional CNS gene: reversal of hypothalmic diabetes insipidus using an EIAV-based lentiviral vector expressing arginine vasopressin. Mol Ther 2003; 7: 588–596.

    Article  CAS  Google Scholar 

  6. Kim H et al. X-gene product of hepatitis B virus induces apoptosis in liver cells. J Biol Chem 273; 1998: 381–385.

    Article  CAS  Google Scholar 

  7. Höhne M et al. Malignant transformation of immortalized transgenic hepatocytes after transfection with hepatitis B virus DNA. EMBO J 9; 1990: 1137–1145.

    Article  Google Scholar 

  8. Schuster R et al. Induction of apoptosis by the transactivating domains of the hepatitis B virus X gene leads to suppression of oncogenic transformation of primary rat embryo fibroblasts. Oncogene 2000; 19: 1173–1180.

    Article  CAS  Google Scholar 

  9. Flajolet M et al. Woodchuck hepatitis virus enhancer I and enhancer II are both involved in N-myc2 activation in woodchuck liver tumours. J Vir 1998; 72: 6175–6180.

    CAS  Google Scholar 

  10. Nash KL et al. Hepatocyte-specific gene expression from integrated lentiviral vectors. J Gene Med 2004; 6: 974–983.

    Article  CAS  Google Scholar 

  11. Terradillos O et al. The hepatitis B virus X gene potentiates c-myc-induced liver oncogenesis in transgenic mice. Oncogene 1997; 14: 395–404.

    Article  CAS  Google Scholar 

  12. Tu H et al. Biological impact of natural COOH-terminal deletions of hepatitis B virus X protein in hepatocellular carcinoma tissues. Cancer Res 2001; 61: 7803–7810.

    CAS  PubMed  Google Scholar 

  13. Sirma H et al. Hepatitis B virus X mutants, present in hepatocellular carcinoma tissue abrogate both the antiproliferative and transactivation effects of HBx. Oncogene 1999; 18: 4848–4859.

    Article  CAS  Google Scholar 

  14. Murakami S et al. Human hepatitis virus X gene encodes a regulatory domain that represses transactivation of X protein. J Biol Chem 1994; 269: 15118–15123.

    CAS  PubMed  Google Scholar 

  15. Azzouz M et al. Neuroprotection of dopamine neurons by non-primate EIAV lentiviral-mediated expression of GDNF in the rat model of Parkinson's disease. Neuroreport 2004; 15: 985–990.

    Article  CAS  Google Scholar 

Download references

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Authors and Affiliations

  1. Oxford BioMedica UK Ltd Medawar Centre, Oxford Science Park, Oxford, UK

    S M Kingsman & K Mitrophanous

  2. Cystic Fibrosis/Pulmonary Research and Treatment Centre, University of North Carolina, Chapel Hill, NC, USA

    J C Olsen

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  1. S M Kingsman
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  2. K Mitrophanous
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  3. J C Olsen
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Kingsman, S., Mitrophanous, K. & Olsen, J. Potential oncogene activity of the woodchuck hepatitis post-transcriptional regulatory element (WPRE). Gene Ther 12, 3–4 (2005). https://doi.org/10.1038/sj.gt.3302417

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