Faculty Collaboration Database

Dissimilar immunogenicities of human papillomavirus E7 and adenovirus E1A proteins influence primary tumor development. Virology 2000 Nov 10;277(1):48-57

Date

11/04/2000

Pubmed ID

11062035

DOI

10.1006/viro.2000.0571

Scopus ID

2-s2.0-0034634327 (requires institutional sign-in at Scopus site)   16 Citations

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.

Author List

Routes JM, Ryan S, Li H, Steinke J, Cook JL

Author

John M. Routes MD Chief, Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

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