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Journal of Virology, April 2003, p. 4928-4937, Vol. 77, No. 8
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.8.4928-4937.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

A Synthetic E7 Gene of Human Papillomavirus Type 16 That Yields Enhanced Expression of the Protein in Mammalian Cells and Is Useful for DNA Immunization Studies

Angel Cid-Arregui,1* Victoria Juárez,2 and Harald zur Hausen1

Angewandte Tumorvirologie, Deutsches Krebsforschungszentrum, D-69120 Heidelberg,1 European Molecular Biology Laboratory, D-69012 Heidelberg, Germany2

Received 26 September 2002/ Accepted 16 January 2003

A synthetic E7 gene of human papillomavirus (HPV) type 16 was generated that consists entirely of preferred human codons. Expression analysis of the synthetic E7 gene in human and animal cells showed levels of E7 protein 20- to 100-fold higher than those obtained with wild-type E7. Enhanced expression of E7 protein resulted from highly efficient translation, as well as increased stability of the E7 mRNA due to its codon optimization. Higher levels of E7 protein in cells transfected with synthetic E7 correlated with significant loss of cell viability in various human cell lines. In contrast, lower E7 protein expression driven by the wild-type gene resulted in a slight induction of cell proliferation. Furthermore, mice inoculated with plasmids expressing the synthetic E7 gene produced significantly higher levels of E7 antibodies than littermates injected with wild-type E7, suggesting that synthetic E7 may be useful for DNA immunization studies and the development of genetic vaccines against HPV-16. In view of these results, we hypothesize that HPVs may have retained a pattern of G + C content and codon usage distinct from that of their host cells in response to selective pressure. Thus, the nonhuman codon bias may have been conserved by HPVs to prevent compromising viability of the host cells by excessive viral early protein expression, as well as to evade the immune system.

* Corresponding author. Mailing address: Angewandte Tumorvirologie, Deutsches Krebsforschungszentrum (DKFZ), Im Neuenheimer Feld 242, D-69120 Heidelberg, Germany. Phone: 49 6221 424917. Fax: 49 6221 424902. E-mail: cid{at}dkfz.de.

Journal of Virology, April 2003, p. 4928-4937, Vol. 77, No. 8
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.8.4928-4937.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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