Document Type

Thesis - University Access Only

Award Date

2006

Degree Name

Master of Science (MS)

Department / School

Biology and Microbiology

Abstract

Dendritic cells (DCs) are considered as a target of vaccine therapy due to their ability to efficiently present antigens to T cells, leading to T cell activation. Previous studies have suggested that murine cytomegalovirus (mCMV) abortively infects human DCs and results in DCs maturation and activation, suggesting the potential utility of mCMV as an antigen delivery vector. In the present study, we further examined the nature of abortive infection that mCMV undergoes in human DCs and the mechanisms of DCs activation by mCMV. Human DCs were prepared from peripheral blood and characterized by immunophenotyping with DCs-specific markers including CD80, CD83, CD86, MHCI, MHCII and CD l le. mCMV DNA synthesis and persistence in human DCs were examined using a real-time PCR. The cytokine profile of mCMV-infected-DCs was determined by a quantitative ELISA and the role of Toll-like receptor 2 (TLR2) and Nuclear Factor Kappa B (NF-kB) in the activation of DCs was investigated. Results showed that mCMV DNA did not accumulate in DCs after infection, suggesting that viral replication is possibly blocked at the viral DNA synthesis step. No viral DNA persistence in DCs was observed. Additionally, mCMV infections of DCs induced the secretions of inflammatory cytokines including TNF-alpha, IL-12, and IL-10. This is in agreement with the activation of NF-kB observed in infected DCs. TLR2 did not appear to have any effect on the activation of NF-kB, but it seemed to play a role in the modulation ofIL-12 and IL-10 cytokines in mCMV-gp 120-infected DCs. Overall, the results suggest that mCMV exhibits some desirable features of a potential viral vector system and warrants further investigations.

Library of Congress Subject Headings

Cytomegaloviruses

Antigens

Viral vaccines

Format

application/pdf

Number of Pages

40

Publisher

South Dakota State University

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