Dissimilar immunogenicities of human papillomavirus E7 and adenovirus E1A proteins influence primary tumor development.

Abstract

Although human papillomaviruses (HPV) and adenoviruses (Ad) both transform cells by expressing functionally related oncogenes (Ad-E1A/E1B; HPV-E7/E6), only HPV are oncogenic in humans. Prior studies have shown that HPV-transformed cells are resistant to NK cell lysis and E7- and E6-specific CTL are inefficiently generated in women with HPV-induced cervical cancer. Therefore, we postulated that the dissimilar oncogenicities of Ad and HPV may be caused by a protective NK and T cell response that is triggered by transformed cells expressing E1A, but not by E7. To test this hypothesis, mice that were either immunologically intact, lacked T cells, or lacked both NK and T cells were challenged with Ad serotype 5 (Ad5)-E1A- or HPV16-E7-transfected tumor cells. E7-expressing tumor cells were resistant to NK cell lysis in vitro and failed to elicit a measurable anti-tumor NK or T cell response in vivo. The concomitant expression of E6 did not change this phenotype. In contrast, E1A-expressing tumor cells were sensitive to NK lysis in vitro and triggered a protective NK and T cell immune response in vivo. These data suggest differences in the capacities of E1A or E7 oncoproteins to trigger protective anti-tumor immune responses may contribute to the dissimilar oncogenicities of Ad and HPV in humans.

• Authors: J M Routes, S Ryan, H Li, J Steinke, J L Cook
• Journal: Virology (Virology) Vol. 277 Issue 1 Pg. 48-57 (Nov 10 2000) ISSN: 0042-6822 [Print] United States
• PMID: 11062035 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)
• Copyright: Copyright 2000 Academic Press.

Chemical References

• Adenovirus E1A Proteins
• Oncogene Proteins, Viral
• Papillomavirus E7 Proteins
• oncogene protein E7, Human papillomavirus type 16

Topics

• Adenovirus E1A Proteins (immunology)
• Adenoviruses, Human (genetics)
• Animals
• Cytotoxicity, Immunologic
• Female
• Fibrosarcoma (immunology, virology)
• Humans
• Killer Cells, Natural (immunology)
• Mice
• Mice, Inbred C57BL
• Mice, Nude
• Mice, Transgenic
• Oncogene Proteins, Viral (immunology)
• Oncogenes
• Papillomaviridae (genetics)
• Papillomavirus E7 Proteins
• Serotyping
• T-Lymphocytes (immunology)
• T-Lymphocytes, Cytotoxic (immunology)
• Tumor Cells, Cultured
• Xenograft Model Antitumor Assays