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Dissertation Information for Sungyoo Cho

NAME:
- Sungyoo Cho

DEGREE:
- Ph.D.

DISCIPLINE:
- Microbiology and Immunology

SCHOOL:
- Indiana University (USA) (2005)

ADVISORS:
- Randy R. Brutkiewicz

COMMITTEE MEMBERS:
- Janice Blum
- Maureen A. Harrington
- Johnny J. He

MPACT Status: Incomplete - Not_Inspected

Title: Immune evasion of CD1d molecules and NKT cells in the innate immune response against viruses

Abstract: CD1d is a MHC class I-like cell surface glycoprotein presenting lipids to T cell subpopulation called natural killer T (NKT) cells. To study the effect of an acute virus infection on NKT cells, mice were infected with the nonhepatotropic Armstrong strain of lymphocytic choriomeningitis virus (LCMV). There was a selective loss of NKT cells in the liver within 3 days post-LCMV and also observed after poly(I:C) treatment. An increase in active caspase 3-specific staining was found in liver NKT cells from LCMV-infected and poly(I:C)-treated mice compared to control and the liver NKT cells were themselves infected. These results suggest that the loss of NKT cells may be due to the induction of IFN-αβ and is important for the host's immune response to LCMV. The HIV-1, protein Nef has immune evasion activity and it causes a decrease in the expression of MHC class I and CD4 molecules. The ability of Nef to alter human CD1d expression was assessed. In vaccinia viruses (VV) co-expressing CD1d and Nef, a substantial reduction in CD1d expression was noticed. Nef had a minimal effect on cell surface expression of the tail-deleted CD1d mutant but physically interacted with wildtype (but not tail-deleted) CD1d. Therefore, an HIV-1 infection may be established by directly interfering with CD1d expression. The murine cytomegalovirus (MCMV) MHC class I homologue m144 has been shown to alter natural killer (NK) cell-mediated control of MCMV replication. We generated a VV expressing m144 (VV-m144). Three days after infection of BALB/c mice with VV-m144, virus titers in the ovaries or spleen were comparable to control and there were no differences in in vitro splenic NK cell activity. The virus titers in the livers of wildtype mice infected with VV-m144 was 10-fold higher than in control, whereas no change in CD1-deficient mice. The lack of NKT cells did not alter the virus titers in VV-m144 infected mice, but a 10 fold higher titer in the control was observed. These results suggest that m144 interferes with NKT cell-dependent viral clearance. Overall, we have found that viruses can evade the host's innate antiviral immune response by targeting CD1d/NKT cell interactions.

MPACT Scores for Sungyoo Cho

A = 0
C = 0
A+C = 0
T = 0
G = 0
W = 0
TD = 0
TA = 0
calculated 2010-10-14 14:19:53

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