Abstract

The mechanism of viral persistence remains a major unresolved problem in virology. The long-term goal of these studies is to understand the mechanisms by which virus evade or suppress the immune response and persist in the host. Persistent viral infections are medically significant because they often have severe consequences in immunosuppressed individuals, and have also been associated with neoplasms and immunopathological diseases. Infection of mice with lymphocytic choriomeningitis virus (LCMV) provides an excellent model for studying the interaction between the virus and the immune system of it's natural host, and in defining conditions that lead to viral clearance or persistence. The objectives of the proposed research are three-fold. First, to analyze the genetic differences between wild type LCMV and LCMV variants, and to map the viral genes that allow the variants to suppress cytotoxic T cell (CTL) responses and cause persistent infections in adult immunocompetent mice. Second, to determine the role of host organs and cell types in selection of unique organ specific virus variants. Third, to examine the interaction of the variants with T cells and macrophages to elucidate the mechanism of CTL suppression. These studies, combining the disciplines of virology and immunology, should provide insight into the genetic basis of viral persistence.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS021496-02
Application #
3402649
Study Section
Virology Study Section (VR)
Project Start
1985-05-01
Project End
1988-04-30
Budget Start
1986-05-01
Budget End
1987-04-30
Support Year
2
Fiscal Year
1986
Total Cost
Indirect Cost

  Institution

Name
University of California Los Angeles
Department
Type
Schools of Medicine
DUNS #
119132785
City
Los Angeles
State
CA
Country
United States
Zip Code
90095

  Publications

Grayson, Jason M; Laniewski, Nathan G; Lanier, J Gibson et al. (2003) Mitochondrial potential and reactive oxygen intermediates in antigen-specific CD8+ T cells during viral infection. J Immunol 170:4745-51
Grayson, Jason M; Harrington, Laurie E; Lanier, J Gibson et al. (2002) Differential sensitivity of naive and memory CD8+ T cells to apoptosis in vivo. J Immunol 169:3760-70
Suresh, M; Lanier, Gibson; Large, Mary Katherine et al. (2002) Role of lymphotoxin alpha in T-cell responses during an acute viral infection. J Virol 76:3943-51
Wu-Hsieh, B A; Whitmire, J K; de Fries, R et al. (2001) Distinct CD8 T cell functions mediate susceptibility to histoplasmosis during chronic viral infection. J Immunol 167:4566-73
Puglielli, M T; Zajac, A J; van der Most, R G et al. (2001) In vivo selection of a lymphocytic choriomeningitis virus variant that affects recognition of the GP33-43 epitope by H-2Db but not H-2Kb. J Virol 75:5099-107
Grayson, J M; Lanier, J G; Altman, J D et al. (2001) The role of p53 in regulating antiviral T cell responses. J Immunol 167:1333-7
Grayson, J M; Murali-Krishna, K; Altman, J D et al. (2001) Gene expression in antigen-specific CD8+ T cells during viral infection. J Immunol 166:795-9
Whitmire, J K; Murali-Krishna, K; Altman, J et al. (2000) Antiviral CD4 and CD8 T-cell memory: differences in the size of the response and activation requirements. Philos Trans R Soc Lond B Biol Sci 355:373-9
Grayson, J M; Zajac, A J; Altman, J D et al. (2000) Cutting edge: increased expression of Bcl-2 in antigen-specific memory CD8+ T cells. J Immunol 164:3950-4
Harrington, L E; Galvan, M; Baum, L G et al. (2000) Differentiating between memory and effector CD8 T cells by altered expression of cell surface O-glycans. J Exp Med 191:1241-6

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