The specific aims of this proposal concern the characterization of properties of a variety of herpesviruses that lead to latency and transformation. The properties of latent and transformed cells will be characterized in efforts to understand why tumor cells metastasize and investigations are in progress to devise methods to control metastases. In addition, experiments will be carried out in attempts to cure latently infected cells. Scientific disciplines involved include those of cell culture, virology, molecular biology, genetics, immunology, cell biology, neurology and oncology. These studies will involve characterization of virus nucleic acids, and their structure, detection of nucleic acids in latent and transformed cells by a variety of techniques including in situ hybridization and Southern and northern blotting procedures and detection of virus-specified proteins by immunofluorescence, immunoprecipitation, and other serologic techniques. These studies are health-related because they deal with ubiquitous viruses found throughout the animal kingdom, including five pathogenic herpesviruses found in man. These viruses are known to cause latent infection in their natural host and to induce naturally causing cancers in a number of animal species that have been carefully examined. Their association with a number of human neoplasms (nasopharyngeal carcinoma, Burkitt lymphoma, cervical cancer, Kaposi sarcoma, prostatic carcinoma) has been well documented; some of these tumors have been shown to carry partial genomes of the viruses to be studied. Experimental models will be employed in the areas where studies with humans are not possible. Ultimately, these studies should enable better understanding of how herpesviruses cause latent and chronic infections and cancer. Information being obtained in this and other projects should provide the means for early diagnosis, for cure, or ultimately, for prevention of the many diseases caused by these viruses.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA027503-08
Application #
3093196
Study Section
Cancer Special Program Advisory Committee (CAK)
Project Start
1980-04-01
Project End
1988-03-31
Budget Start
1987-04-01
Budget End
1988-03-31
Support Year
8
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Pennsylvania State University
Department
Type
Schools of Medicine
DUNS #
129348186
City
Hershey
State
PA
Country
United States
Zip Code
17033
Peng, X; Lang, C M; Kreider, J W (1996) Immortalization of inbred rabbit keratinocytes from a Shope papilloma and tumorigenic transformation of the cells by EJ-ras. Cancer Lett 108:101-9
Peng, X; Lang, C M; Kreider, J W (1995) Methylation of cottontail rabbit papillomavirus DNA and tissue-specific expression in transgenic rabbits. Virus Res 35:101-8
Kenny, J J; Krebs, F C; Hartle, H T et al. (1994) Identification of a second ATF/CREB-like element in the herpes simplex virus type 1 (HSV-1) latency-associated transcript (LAT) promoter. Virology 200:220-35
Samaniego, L A; Tevethia, M J; Spector, D J (1994) The human cytomegalovirus 86-kilodalton immediate-early 2 protein: synthesis as a precursor polypeptide and interaction with a 75-kilodalton protein of probable viral origin. J Virol 68:720-9
Spector, D J; Tevethia, M J (1994) Protein-protein interactions between human cytomegalovirus IE2-580aa and pUL84 in lytically infected cells. J Virol 68:7549-53
Kierstead, T D; Tevethia, M J (1993) Association of p53 binding and immortalization of primary C57BL/6 mouse embryo fibroblasts by using simian virus 40 T-antigen mutants bearing internal overlapping deletion mutations. J Virol 67:1817-29
Peng, X; Olson, R O; Christian, C B et al. (1993) Papillomas and carcinomas in transgenic rabbits carrying EJ-ras DNA and cottontail rabbit papillomavirus DNA. J Virol 67:1698-701
Wisotzkey, J D; Krizenoskas, A; DiAngelo, S et al. (1993) Cleavage of cottontail rabbit papillomavirus E7 RNA with an anti-E7 ribozyme. Biochem Biophys Res Commun 192:833-9
Okabayashi, M; Pickel, M D; Budgeon, L R et al. (1993) Podofilox-induced regression of Shope papillomas may be independent of host immunity. J Invest Dermatol 101:852-7
Bonneau, R H; Salvucci, L A; Johnson, D C et al. (1993) Epitope specificity of H-2Kb-restricted, HSV-1-, and HSV-2-cross-reactive cytotoxic T lymphocyte clones. Virology 195:62-70

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