Construction and characterization of recombinant fowlpox viruses expressing human papilloma virus E6 and E7 oncoproteins.
Human papilloma virus (HPV)-16 is the most prevalent high-risk mucosal genotype and the expression of the E6 and E7 proteins, which can bind to the p53 and p105Rb host cell-cycle regulatory proteins, is related to its tumorigenicity. Virus-like-particle (VLP)-based immunogens developed recently are successful as prophylactic HPV vaccines. However, given the high number of individuals infected already with HPV and the absence of expression of the L1 structural protein in HPV-infected or HPV-transformed cells, an efficient therapeutic vaccine targeting the non-structural E6 and E7 oncoproteins is required. In this study, two new fowlpox virus (FPV) recombinants encoding the HPV-16 E6 and E7 proteins were engineered and evaluated for their correct expression in vitro, with the final aim of developing a therapeutic vaccine against HPV-related cervical tumors. Although vaccinia viruses expressing the HPV-16 and HPV-18 E6 and E7 oncoproteins have already been studied, due to their natural host-range restriction to avian species and their ability to elicit a complete immune response, FPV recombinants may represent efficient and safer vectors also for immunocompromised hosts. The results indicate that FPV recombinants can express correctly the E6 and E7 oncoproteins, and they should represent appropriate vectors for the expression of these oncoproteins in human cells.
Department of Medical Pharmacology, University of Milan, Milan, Italy.
Eleana
E
Pozzi
Valeria
V
Basavecchia
Carlo
C
Zanotto
Sole
S
Pacchioni
Carlo De Giuli
Cde G
Morghen
Antonia
A
Radaelli
D000818:Animals; D002460:Cell Line; D005587:Fowlpox virus / Q000235:genetics*; D015870:Gene Expression; D005822:Genetic Vectors; D006801:Humans; D009856:Oncogene Proteins, Viral / Q000235:genetics*; D050725:Papillomavirus E7 Proteins; D053918:Papillomavirus Vaccines / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics*; D014614:Vaccines, Synthetic / Q000235:genetics
C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D053918:Papillomavirus Vaccines; D012097:Repressor Proteins; D014614:Vaccines, Synthetic; C059731:oncogene protein E7, Human papillomavirus type 16