Hypoxic-response elements in the oncolytic parvovirus do not allow for increased vector production at low oxygen concentration Free

Abstract

Vectors derived from the autonomous parvovirus , MVM(p), are promising tools for the gene therapy of cancer. The validation of their anti-tumour effect is, however, hampered by the difficulty to produce high-titre stocks. In an attempt to increase vector titres, host cells were subjected to low oxygen tension (hypoxia). It has been shown that a number of viruses are produced at higher titres under these conditions. This is the case, among others, for another member of the family , the erythrovirus . Hypoxia stabilizes a hypoxia-inducible transcription factor (HIF-1) that interacts with a ‘hypoxia-responsive element’ (HRE), the consensus sequence of which (/CGTG) is present in the B19 and MVM promoters. Whilst the native P4 promoter was induced weakly in hypoxia, vector production was reduced dramatically, and adding HRE elements to the P4 promoter of the vector did not alleviate this reduction. Hypoxia has many effects on cell metabolism. Therefore, even if the P4 promoter is activated, the cellular factors that are required for the completion of the parvoviral life cycle may not be expressed.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.81754-0
2006-05-01
2024-03-28
Loading full text...

Full text loading...

/deliver/fulltext/jgv/87/5/1197.html?itemId=/content/journal/jgv/10.1099/vir.0.81754-0&mimeType=html&fmt=ahah

References

  1. Astell C. R., Gardiner E. M., Tattersall P. 1986; DNA sequence of the lymphotropic variant of minute virus of mice, MVM(i), and comparison with the DNA sequence of the fibrotropic prototype strain. J Virol 57:656–669
    [Google Scholar]
  2. Brandenburger A., Velu T. 2004; Autonomous parvovirus vectors : preventing the generation of wild-type or replication-competent virus. J Gene Med 6:S203–S211 [CrossRef]
    [Google Scholar]
  3. Caillet-Fauquet P., Perros M., Brandenburger A., Spegelaere P., Rommelaere J. 1990; Programmed killing of human cells by means of an inducible clone of parvoviral genes encoding non-structural proteins. EMBO J 9:2989–2995
    [Google Scholar]
  4. Caillet-Fauquet P., Draps M.-L., Di Giambattista M., de Launoit Y., Laub R. 2004; Hypoxia enables B19 erythrovirus to yield abundant infectious progeny in a pluripotent erythroid cell line. J Virol Methods 121:145–153 [CrossRef]
    [Google Scholar]
  5. Cheong S. C., Clément N., Velu T., Brandenburger A. 2003; A novel method for the titration of recombinant virus stocks by ELISPOT assay. J Virol Methods 109:119–124 [CrossRef]
    [Google Scholar]
  6. Clément N., Velu T., Brandenburger A. 2002; Construction and production of oncotropic vectors, derived from MVM(p), that share reduced sequence homology with helper plasmids. Cancer Gene Ther 9:762–770 [CrossRef]
    [Google Scholar]
  7. Cornelis J. J., Lang S. I., Stroh-Dege A. Y., Balboni G., Dinsart C., Rommelaere J. 2004; Cancer gene therapy through autonomous parvovirus-mediated gene transfer. Curr Gene Ther 4:249–261 [CrossRef]
    [Google Scholar]
  8. Cotmore S. F., Sturzenbecker L. J., Tattersall P. 1983; The autonomous parvovirus MVM encodes two nonstructural proteins in addition to its capsid polypeptides. Virology 129:333–343 [CrossRef]
    [Google Scholar]
  9. Davis D. A., Rinderknecht A. S., Zoeteweij J. P., Aoki Y., Read-Connole E. L., Tosato G., Blauvelt A., Yarchoan R. 2001; Hypoxia induces lytic replication of Kaposi sarcoma-associated herpesvirus. Blood 97:3244–3250 [CrossRef]
    [Google Scholar]
  10. Ebbesen P., Zachar V. 1998; Oxygen tension and virus replication. Acta Virol 42:417–421
    [Google Scholar]
  11. Ebbesen P., Toth F. D., Villadsen J. A., Norskov-Lauritsen N. 1991; In vitro interferon and virus production at in vivo physiologic oxygen tensions. In Vivo 5:355–358
    [Google Scholar]
  12. Huang L. E., Arany Z., Livingston D. M., Bunn H. F. 1996; Activation of hypoxia-inducible transcription factor depends primarily upon redox-sensitive stabilization of its α subunit. J Biol Chem 271:32253–32259 [CrossRef]
    [Google Scholar]
  13. Jeong C. H., Lee Y. M., Choi K. S., Seong Y. R., Kim Y. J., Im D. S., Kim K. W. 2005; Hypoxia-responsive element-mediated soluble Tie2 vector exhibits an anti-angiogenic activity in vitro under hypoxic condition. Int J Oncol 26:211–216
    [Google Scholar]
  14. Menon C., Fraker D. L. 2005; Tumor oxygenation status as a prognostic marker. Cancer Lett 221:225–235 [CrossRef]
    [Google Scholar]
  15. Mottet D., Michel G., Renard P., Ninane N., Raes M., Michiels C. 2003; Role of ERK and calcium in the hypoxia-induced activation of HIF-1. J Cell Physiol 194:30–44 [CrossRef]
    [Google Scholar]
  16. Nüesch J. P. F., Dettwiler S., Corbeau R., Rommelaere J. 1998; Replicative functions of minute virus of mice NS1 protein are regulated in vitro by phosphorylation through protein kinase C. J Virol 72:9966–9977
    [Google Scholar]
  17. Pillet S., Le Guyader N. 2005; Interaction des virus avec la voie cellulaire de réponse à l'hypoxie. Med Sci (Paris) 21:517–522 (in French [CrossRef]
    [Google Scholar]
  18. Pillet S., Le Guyader N., Hofer T., NguyenKhac F., Koken M., Aubin J.-T., Fichelson S., Gassmann M., Morinet F. 2004; Hypoxia enhances human B19 erythrovirus gene expression in primary erythroid cells. Virology 327:1–7 [CrossRef]
    [Google Scholar]
  19. Pipiya T., Sauthoff H., Huang Y. Q., Chang B., Cheng J., Heitner S., Chen S., Rom W. N., Hay J. G. 2005; Hypoxia reduces adenoviral replication in cancer cells by downregulation of viral protein expression. Gene Ther 12:911–917 [CrossRef]
    [Google Scholar]
  20. Polonis V. R., Anderson G. R., Vahey M. T., Morrow P. J., Stoler D., Redfield R. R. 1991; Anoxia induces human immunodeficiency virus expression in infected T cell lines. J Biol Chem 266:11421–11424
    [Google Scholar]
  21. Rhode S. L. III 1985; trans -Activation of parvovirus P38 promoter by the 76K noncapsid protein. J Virol 55:886–889
    [Google Scholar]
  22. Riedinger H.-J., van Betteraey M., Probst H. 1999; Hypoxia blocks in vivo initiation of simian virus 40 replication at a stage preceding origin unwinding. J Virol 73:2243–2252
    [Google Scholar]
  23. Rommelaere J., Cornelis J. J. 1991; Antineoplastic activity of parvoviruses. J Virol Methods 33:233–251 [CrossRef]
    [Google Scholar]
  24. Ruan H., Su H., Hu L., Lamborn K. R., Kan Y. W., Deen D. F. 2001; A hypoxia-regulated adeno-associated virus vector for cancer-specific gene therapy. Neoplasia 3:255–263 [CrossRef]
    [Google Scholar]
  25. Russell S. J., Brandenburger A., Flemming C. L., Collins M. K. L., Rommelaere J. 1992; Transformation-dependent expression of interleukin genes delivered by a recombinant parvovirus. J Virol 66:2821–2828
    [Google Scholar]
  26. Semenza G. L. 2001; HIF-1, O2, and the 3 PHDs: how animal cells signal hypoxia to the nucleus. Cell 107:1–3 [CrossRef]
    [Google Scholar]
  27. Shen B. H., Hermiston T. W. 2005; Effect of hypoxia on Ad5 infection, transgene expression and replication. Gene Ther 12:902–910 [CrossRef]
    [Google Scholar]
  28. Shibata T., Giaccia A. J., Brown J. M. 2000; Development of a hypoxia-responsive vector for tumor-specific gene therapy. Gene Ther 7:493–498 [CrossRef]
    [Google Scholar]
  29. Wang G. L., Semenza G. L. 1995; Purification and characterization of hypoxia-inducible factor 1. J Biol Chem 270:1230–1237 [CrossRef]
    [Google Scholar]
  30. Wang D., Ruan H., Hu L., Lamborn K. R., Kong E. L., Rehemtulla A., Deen D. F. 2005; Development of a hypoxia-inducible cytosine deaminase expression vector for gene-directed prodrug cancer therapy. Cancer Gene Ther 12:276–283 [CrossRef]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.81754-0
Loading
/content/journal/jgv/10.1099/vir.0.81754-0
Loading

Data & Media loading...

Supplements

Supplementary material 1

PDF

Most cited Most Cited RSS feed