Abstract

This proposal has two major specific aims: 1) To demonstrate the existence HCV-specific liver-infiltrating cytotoxic T lymphocytes in chronic HCV infection. The applicant has already determined the HCV genotype of many patients and will complete this. To detect the presence of HCV-specific CTLs, he will employ a target cell consisting EBV immortalized B-lymphoblastoid cells from each patient with chronic HCV. These cells will be infected with vaccinia virus carrying HCV gene inserts coding for specific candidate regions that are suspected of serving as epitopes in the CTL recognition process. CTLs will be obtained by bulk expansion of lymphocytes harvested from liver biopsies. chromium release assay of target cell lysis will be used to detect cells and quantitate the cytotoxic activity. 2) The second specific aim is to define the actual epitopes involved in the CTL- mediated recognition. CTLs identified in specific aim 1 will be cloned for use in screening small synthetically produced peptides overlapping in regions identified in specific aim 1. Sensitization of target cells and the cytolysis assay will be used.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI041219-03
Application #
2672978
Study Section
General Medicine A Subcommittee 2 (GMA)
Project Start
1996-09-01
Project End
2000-08-31
Budget Start
1998-09-01
Budget End
1999-08-31
Support Year
3
Fiscal Year
1998
Total Cost
Indirect Cost

  Institution

Name
University of Florida
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
073130411
City
Gainesville
State
FL
Country
United States
Zip Code
32611

  Publications

Fang, Jane W S; Gonzalez-Peralta, Regino P; Chong, Sonny K F et al. (2011) Hepatic expression of cell proliferation markers and growth factors in giant cell hepatitis: implications for the pathogenetic mechanisms involved. J Pediatr Gastroenterol Nutr 52:65-72
Xie, X; Forsmark, C E; Lau, J Y (2000) Effect of bile and pancreatic juice on adenoviral-mediated gene delivery: implications on the feasibility of gene delivery through ERCP. Dig Dis Sci 45:230-6
Liu, K; Kao, K J (2000) Mechanisms for genetically predetermined differential quantitative expression of HLA-A and -B antigens. Hum Immunol 61:799-807
Slimane, S B; Albrecht, J K; Fang, J W et al. (2000) Clinical, virological and histological implications of GB virus-C/hepatitis G virus infection in patients with chronic hepatitis C virus infection: a multicentre study based on 671 patients. J Viral Hepat 7:51-5
Reiser, M; Neumann, I; Schmiegel, W et al. (2000) Induction of cell proliferation arrest and apoptosis in hepatoma cells through adenoviral-mediated transfer of p53 gene. J Hepatol 32:771-82
Qian, K P; Natov, S N; Pereira, B J et al. (2000) Hepatitis C virus mixed genotype infection in patients on haemodialysis. J Viral Hepat 7:153-60
Dickson, R C; Mizokami, M; Orito, E et al. (1999) Quantification of serum HCV core antigen by a fluorescent enzyme immunoassay in liver transplant recipients with recurrent hepatitis C--clinical and virologic implications. Transplantation 68:1512-6
Gish, R G; Qian, K; Brooks, L et al. (1999) Characterization of anti-hepatitis C virus-positive sera not genotyped by restriction fragment length polymorphism or serology. J Gastroenterol Hepatol 14:339-44
Isaacson, A H; Bhardwaj, B; Qian, K et al. (1999) Hepatitis G virus infection in renal transplant recipients. J Viral Hepat 6:151-60
Mizokami, M; Ohno, T; Ohba, K et al. (1999) Interferon-alpha therapy exerts selective pressure on hepatitis C virus quasispecies equilibrium. Antivir Ther 4:15-9

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