The Epstein-Barr virus (EBV) has been studied extensively as a causative agent of some forms of human cancer. These investigations have included immunological studies on patients with EBV-associated cancers and on tumor tissues suspected to harbor the EBV genome. Such studies have resulted in the identification of antibodies to specific EBV antigens that are of diagnostic and prognostic importance in patients with EBV- associated diseases and in the identification of some of the antigens important in immunity to the virus-infected or transformed cells. Until recently, however, little was known about the composition of the different EBV antigen complexes. This laboratory has focused on the identification and characterization of the native polypeptides associated with the different EBV antigen complexes over the past 11 years through the support of this NCI grant. These studies have resulted in the identification of the major polypeptides associated with the EBV- induced membrane antigen (MA), viral capsid antigen (VCA) and early antigen (EA) complexes. These polypeptides have been mapped to specific fragments of EBV DNA and the biological activity associated with some of these polypeptides has been identified. Monoclonal antibodies have been generated to all of the polypeptides which have been used by numerous investigators working on EBV.
The specific aims of this renewal proposal for years 12-16 are: (1) to continue to identify and fully characterize polypeptides associated with each of these major antigen complexes and to utilize the purified polypeptide in different immunological studies; (2) to attempt to determine the importance of polypeptides associated with these different antigen complexes in the induction of T-cell immunity against the virus-infected or transformed cell; (3) to continue to determine if the prognostic importance of antibody measured by the ADCC is assay related to the presence of IgA antibodies to specific epitopes expressed on the major MA glycoprotein; (4) to perform ultrastructural studies to determine the biological significance of the cytoplasmic filamentous structures associated with the restricted (R) component of the EA complex; and (5) to continue to collaborate with other investigators using our monoclonal reagents. Completion of these studies will lead to a better understanding of the nature of the viral proteins important to the development of both humoral and cellular immunity to the virus- infected and transformed cells and could lead to the development of new approaches for the prevention or treatment of EBV- associated diseases.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA039617-08
Application #
3178816
Study Section
Virology Study Section (VR)
Project Start
1984-07-01
Project End
1993-04-30
Budget Start
1991-05-01
Budget End
1992-04-30
Support Year
8
Fiscal Year
1991
Total Cost
Indirect Cost
Name
Georgetown University
Department
Type
Schools of Dentistry
DUNS #
049515844
City
Washington
State
DC
Country
United States
Zip Code
20057
Durda, P J; Sullivan, M; Kieff, E et al. (1993) An enzyme-linked immunosorbent assay for the measurement of human IgA antibody responses to Epstein-Barr virus membrane antigen. Intervirology 36:11-9
Pothen, S; Richert, J R; Pearson, G R (1991) Human T-cell recognition of Epstein-Barr virus-induced replication antigen complexes. Int J Cancer 49:656-60
Kocache, M M; Pearson, G R (1990) Protein kinase activity associated with a cell cycle regulated, membrane-bound Epstein-Barr virus induced early antigen. Intervirology 31:1-13
Goldschmidts, W L; Ginsburg, M; Pearson, G R (1989) Neutralization of Epstein-Barr virus-induced ribonucleotide reductase with antibody to the major restricted early antigen polypeptide. Virology 170:330-3
Luka, J; Deeb, Z E; Hartmann, D P et al. (1988) Detection of antigens associated with Epstein-Barr virus replication in extracts from biopsy specimens of nasopharyngeal carcinomas. J Natl Cancer Inst 80:1164-7
Goldschmidts, W; Luka, J; Pearson, G R (1987) A restricted component of the Epstein-Barr virus early antigen complex is structurally related to ribonucleotide reductase. Virology 157:220-6
Pearson, G R; Luka, J; Petti, L et al. (1987) Identification of an Epstein-Barr virus early gene encoding a second component of the restricted early antigen complex. Virology 160:151-61
Emini, E A; Luka, J; Armstrong, M E et al. (1987) Identification of an Epstein-Barr virus glycoprotein which is antigenically homologous to the varicella-zoster virus glycoprotein II and the herpes simplex virus glycoprotein B. Virology 157:552-5
Pearson, G R (1986) The Epstein-Barr virus genome and phenotypic expression during lytic cycle. AIDS Res 2 Suppl 1:S49-56
Emini, E A; Luka, J; Armstrong, M E et al. (1986) Establishment and characterization of a chronic infectious mononucleosislike syndrome in common marmosets. J Med Virol 18:369-79

Showing the most recent 10 out of 11 publications