The long-term goal of these studies is to understand the mechanisms by which viruses evade or suppress the immune response and persist in the host. The mechanism of viral persistence remains a major unresolved problem in virology. While the reported incidence of several acute viral infections has declined in recent years, the incidence of persistent viral infections has been increasing. This is most dramatically illustrated by the acquired immune deficiency syndrome (AIDS). Chronic hepatitis B virus infections have also steadily increased with current estimates of over 200 million virus carriers. In addition, persistent viral infections have been associated with certain 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 two-fold. First, to analyze the genetic differences between wild type LCMV and LCMV variants and to identify the precise location of the mutations that allow these varients to suppress virus specific T cell responses and cause persistent infections in adult mice. Second, to examine the interaction of the variants with T cells and macrophages to elucidate the mechanism of immunosuppression. These studies, combining the disciplines of virology and immunology, should lead to an improved fundamental understanding of the pathogenesis of chronic viral infections

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
2R01NS021496-04
Application #
3402647
Study Section
Virology Study Section (VR)
Project Start
1985-05-01
Project End
1993-04-30
Budget Start
1988-05-01
Budget End
1989-04-30
Support Year
4
Fiscal Year
1988
Total Cost
Indirect Cost
Name
University of California Los Angeles
Department
Type
Schools of Medicine
DUNS #
119132785
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
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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
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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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