1887

Journal of General Virology header logo

Volume 78, Issue 7

Comparison of the human versus murine cytomegalovirus immediate early gene promoters for transgene expression by adenoviral vectors Free

Abstract

We have developed a number of replication defective adenoviral (Ad) vectors which express transgenes under the control of the human cytomegalovirus (HCMV) immediate early (IE) gene promoter. The orientation of the expression cassette replacing E1 in the vector backbone had a significant effect on the level of transgene expression, with vectors containing expression cassettes directed towards the right end of the Ad genome expressing 7-fold higher levels of -galactosidase (-gal) than those with inserts in the opposite orientation. Murine cells infected with any of several different Ad vectors in which transgene expression was under the control of the HCMV IE promoter produced 10–100-fold less transgene product (such as -gal) than similarly infected human cells. Replacing the HCMV IE promoter with the murine CMV (MCMV) IE promoter resulted in an increase in the levels of -gal produced in murine and rat cells by approximately 5–30-fold compared to levels obtained with the HCMV IE promoter, and levels produced in human cells were the same or greater using the MCMV IE promoter compared to the HCMV IE promoter. Similar results were obtained using a luciferase reporter gene. The MCMV IE promoter, therefore, was able to drive high levels of expression without the pronounced species preferences observed for the HCMV IE promoter. The MCMV IE promoter also directed high levels of expression , suggesting that Ad vectors carrying the MCMV IE promoter may be more effective than those with the HCMV IE promoter for transgene expression in animal models.

  • Published Online:
© Society for General Microbiology Ltd 1997
Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-78-7-1653
1997-07-01
2024-04-19
Loading full text...

Full text loading...

/deliver/fulltext/jgv/78/7/9225042.html?itemId=/content/journal/jgv/10.1099/0022-1317-78-7-1653&mimeType=html&fmt=ahah

References

  1. Addison C. L., Braciak T., Ralston R., Muller W. J., Gauldie J., Graham F. L. 1995a; Intra-tumoral injection of an adenovirus expressing interleukin-2 induces regression and immunity in a murine breast cancer model. Proceedings of the National Academy of Sciences USA: 928522–8526
     [Google Scholar]
  2. Addison C. L., Gauldie J., Muller W. J., Graham F. L. 1995b; An adenoviral vector expressing interleukin-4 modulates tumorigenicity and induces regression in a murine breast cancer model. International Journal of Oncology 7:1253–1260
     [Google Scholar]
  3. Anton M., Graham F. L. 1995; Site-specific recombination mediated by an adenovirus vector expressing the cre recombinase protein: a molecular switch for control of gene expression. Journal of Virology 69:4600–4606
     [Google Scholar]
  4. Baskar J. F., Smith P., Ciment G. S., Hoffmann S., Tucker C., Tenney D. J., Colberg-Poley A. M., Nelson J. A., Ghazal P. 1996a; .Developmental analysis of the cytomegalovirus enhancer in transgenic animals. Journal of Virology 70:3215–3226
     [Google Scholar]
  5. Baskar J. F., Smith P. P., Nilaver G., Jupp R. A., Hoffmann S., Peffer N. J., Tenney D. J., Colberg-Poley A. M., Ghazal P., Nelson J. A. 1996b; The enhancer domain of the human cytomegalovirus major immediate-early promoter determines cell type-specific expression in transgenic mice. Journal of Virology 70:3207–3214
     [Google Scholar]
  6. Bett A. J. 1995; Construction and characterization of recombinant human adenovirus type 5 vectors. PhD thesis McMaster University; Hamilton, Ontario, Canada:
     [Google Scholar]
  7. Bett A. J., Haddara W., Prevec L., Graham F. L. 1994; An efficient and flexible system for construction of adenovirus vectors with insertions or deletions in early regions 1 and 3. Proceedings of the National Academy of Sciences USA: 918802–8806
     [Google Scholar]
  8. Boshart M., Weber F., Jahn G., Dorsch-Hasler K., Fleckenstein B., Schaffner W. 1985; A very strong enhancer is located upstream of an immediate early gene of human cytomegalovirus. Cell 41:521–530
     [Google Scholar]
  9. Bramson J., Hitt M., Addison C. L., Muller W. J., Gauldie J., Graham F. L. 1996a; Direct intratumoral injection of an adenovirus expressing interleukin-12 induces regression and long-lasting immunity that is associated with highly localized expression of interleukin-12. Human Gene Therapy 7:1995–2002
     [Google Scholar]
  10. Bramson J., Hitt M., Gallichan W. S., Rosenthal K. L., Gauldie J., Graham F. L. 1996b; Construction of a double recombinant adenovirus vector expressing a heterodimeric cytokine : in vitro and in vivo production of biologically active interleukin-12. Human Gene Therapy 7:333–342
     [Google Scholar]
  11. DeWet J. R., Wood K. V., DeLuca M., Helinski D. R., Subramani S. 1987; Firefly luciferase gene: structure and expression in mammalian cells. Molecular and Cellular Biology 7:725–737
     [Google Scholar]
  12. Dorsch-Hasler K., Keil G. M., Weber F., Jasin M., Schaffner W., Koszinowski U. H. 1985; A long and complex enhancer activates transcription of the gene coding for the highly abundant immediate early mRNA in murine cytomegalovirus. Proceedings of the National Academy of Sciences USA: 828325–8329
     [Google Scholar]
  13. Engelhardt J. F., Ye X., Doranz B., Wilson J. M. 1994; Ablation of E2A in recombinant adenoviruses improves transgene persistence and decreases inflammatory response in mouse liver. Proceedings of the National Academy of Sciences USA: 916196–6200
     [Google Scholar]
  14. Fickenscher H., Stamminger T., Ruger R., Fleckenstein B. 1989; The role of repetitive palindromic sequence elements in the human cytomegalovirus immediate early enhancer. Journal of General Virology 70:107–123
     [Google Scholar]
  15. Fidler I. J. 1975; Biological behaviour of malignant melanoma cells correlated to their survival in vivo. Cancer Research 35:218–234
     [Google Scholar]
  16. Gerard R. D., Meidell R. S. 1995; Adenovirus vectors. In DNA Cloning: A Practical Approach pp 285–306 Hames B. D., Glover D. Edited by Oxford: Oxford University Press;
     [Google Scholar]
  17. Ghazal P., Lubon H., Hennighausen L. 1988; Multiple sequence- specific transcription factors modulate cytomegalovirus enhancer activity in vitro. Molecular and Cellular Biology 8:1809–1811
     [Google Scholar]
  18. Graham F. L., Smiley J., Russell W. C., Nairn R. 1977; Characteristics of a human cell line transformed by DNA from human adenovirus type 5. Journal of General Virology 36:59–72
     [Google Scholar]
  19. Guy C. T., Cardiff R. D., Muller W. J. 1992; Induction of mammary tumors by expression of polyomavirus middle T oncogene : a transgenic mouse model for metastatic disease. Molecular and Cellular Biology 12:954–961
     [Google Scholar]
  20. Hennighausen L., Fleckenstein B. 1986; Nuclear factor 1 interacts with five DNA elements in the promoter region of the human cytomegalovirus major immediate early gene. EMBO Journal 5:1367–1371
     [Google Scholar]
  21. Herlyn M., Thurin J., Balaban G., Bennicelli J. L., Herlyn D., Elder D. E., Bondi E., Guerry D., Nowell P., Clark W. H., Koprowski H. 1985; Characteristics of cultured human melanocytes isolated from different stages of tumor progression. Cancer Research 45:5670–5676
     [Google Scholar]
  22. Hitt M., Bett A. J., Addison C. L., Prevec L., Graham F. L. 1995; Techniques for human adenovirus vector construction and characterization. Methods in Molecular Genetics 7:13–30
     [Google Scholar]
  23. Hunninghake G. W., Monick M. M., Liu B., Stinski M. F. 1989; The promoter-regulatory region of the major immediate-early gene of human cytomegalovirus responds to T-lymphocyte stimulation and contains functional cyclic AMP-response elements. Journal of General Virology 63:3026–3033
     [Google Scholar]
  24. Kothary R., Barton S. C., Franz T., Norris M. L., Hettle S., Surani M. A. H. 1991; Unusual cell specific expression of a major human cytomegalovirus immediate early gene promoter-lacZ hybrid gene in transgenic mouse embryos. Mechanisms of Development 35:25–31
     [Google Scholar]
  25. Kozak M. 1991; Structural features in eukaryotic mRNAs that modulate the initiation of translation. Journal of Biological Chemistry 266:19867–19870
     [Google Scholar]
  26. Lafemina R. L., Hayward G. S. 1988; Differences in cell type- specific blocks to immediate early gene expression and DNA replication of human, simian, andmurine cytomegalovirus. JournalofGeneral Virology 69:355–374
     [Google Scholar]
  27. McGrory W. J., Bautista D., Graham F. L. 1988; A simple technique for the rescue of early region I mutations into infectious human adenovirus type 5. Virology 163:614–617
     [Google Scholar]
  28. Mittal S. K., McDermott M. R., Johnson D. C., Prevec L., Graham F. L. 1993; Monitoring foreign gene expression by a human adenovirus-based vector using the firefly luciferase gene as a reporter. Virus Research 28:67–90
     [Google Scholar]
  29. Nelson J. A., Groudine M. 1986; Transcriptional regulation of the human cytomegalovirus immediate-early gene is associated with in-duction of DNaseI-hypersensitive sites. Molecular and Cellular Biology 6:452–461
     [Google Scholar]
  30. Niller H. H., Hennighausen L. 1991; Formation of several specific nucleoprotein complexes on the human cytomegalovirus immediate early enhancer. Nucleic Acids Research 19:3715–3721
     [Google Scholar]
  31. Parks R. J., Chen L., Anton M., Sankar U., Rudnicki M. A., Graham F. L. 1996; A helper-dependent adenovirus vector system: removal of helper virus by cre-mediated excision of the viral packaging signal. Proceedings of the National Academy of Sciences USA: 9313565–13570
     [Google Scholar]
  32. Sambrook J., Fritsch E. F., Maniatis T. 1989; . Molecular Cloning: A Laboratory Manual, 2nd edn.. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory;
     [Google Scholar]
  33. Sambucetti L. C., Cherrington J. M., Wilkinson G. W. G., Mocarski E. S. 1989; NF-kB activation of the cytomegalovirus enhancer is mediated by a viral transactivator and by T cell stimulation. EMBO Journal 8:4251–4258
     [Google Scholar]
  34. Schmidt E. V., Christoph G., Zeller R., Leder P. 1990; The cytomegalovirus enhancer: a pan-active control element in transgenic mice. Molecular and Cellular Biology 10:4406–4411
     [Google Scholar]
  35. Stamminger T., Fickenscher H., Fleckenstein B. 1990; Cell-type- specific induction of the major immediate-early enhancer of human cytomegalovirus by cyclic AMP. Journal ofGeneral Virology 71:105–113
     [Google Scholar]
  36. Stinski M. F. 1990; Cytomegalovirus and its replication. In Virology, 2nd edn.. pp 1959–1980 Fields B. N., Knipe D. M. Edited by New York: Raven Press;
     [Google Scholar]
  37. Wilkinson G. W. G., Akrigg A. 1992; Constitutive and enhanced expression from the CMV major IE promoter in a defective adenovirus vector. Nucleic Acids Research 20:2233–2239
     [Google Scholar]
  38. Xu Z. Z., Krougliak V., Prevec L., Graham F. L., Both G. W. 1995; Investigation of promoter function in human and animal cells infected with human recombinant adenoviruses expressing rotavirus antigen VP7sc. Journal of General Virology 76:1971–1980
     [Google Scholar]
  39. Yang Y., Nunes F. A., Berencsi K., Furth E. E., Gonczol E., Wilson J. M. 1994; Cellular immunity to viral antigens limits E1-deleted adenoviruses for gene therapy. Proceedings of the National Academy of Sciences USA: 914407–4411
     [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-78-7-1653
Loading
Comparison of the human versus murine cytomegalovirus immediate early gene promoters for transgene expression by adenoviral vectors
J. Gen. Virol. 78, 1653 (1997); https://doi.org/10.1099/0022-1317-78-7-1653
/content/journal/jgv/10.1099/0022-1317-78-7-1653
/content/journal/jgv/10.1099/0022-1317-78-7-1653
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