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dc.contributor.authorKing, Christine April.en_US
dc.date.accessioned2014-10-21T12:37:52Z
dc.date.available2003
dc.date.issued2003en_US
dc.identifier.otherAAINQ79392en_US
dc.identifier.urihttp://hdl.handle.net/10222/55892
dc.descriptionDengue virus, family Flaviviridae, is thought to be the most important vector-borne disease as it is estimated that 100 million individuals are infected with dengue virus annually.en_US
dc.descriptionWe investigated the ability of dengue virus to infect mast cells and the resultant response. We have shown that human mast cell lines, KU812 and HMC-1, are permissive to antibody-enhanced dengue virus infection and that infection is dependent on FcgammaRII-mediated binding. Antibody-enhanced dengue virus infection resulted in infectious virus production as well as induction of significant levels of IL-1beta and IL-6. Moreover, elevated levels of secreted RANTES, MIP-1alpha, and MIP-1beta, but not IL-8 or ENA-78, were observed following infection of KU812 or HMC-1 cells. In some cases a greater than 200 fold increase in RANTES production was observed in response to dengue virus infection. Primary cultures of cord blood derived human mast cells (CBMCs) treated with dengue virus in the presence of sub-neutralizing concentrations of dengue specific antibody also demonstrated significantly (p < 0.05) increased RANTES production, under conditions which did not induce significant short-term degranulation. In addition, we have shown IFN-gamma treated CBMCs expressed higher levels of FcgammaRI and FcgammaRIII and enhanced RANTES production. Chemokine responses were not observed when mast cells were treated with UV-inactivated dengue virus in the presence or absence of human dengue specific antibody suggesting the response is dependent on active infection.en_US
dc.descriptionThe mast cell response to dengue virus appears to be highly selective and specific as neither antibody-enhanced dengue virus infection of the highly permissive U937 monocytic cell line, nor adenovirus infection of mast cells, induced RANTES, MIP-1alpha, or MIP-1beta. These results suggest a role for mast cells in the initiation of chemokine-dependent host responses to viral infection.en_US
dc.descriptionThesis (Ph.D.)--Dalhousie University (Canada), 2003.en_US
dc.languageengen_US
dc.publisherDalhousie Universityen_US
dc.publisheren_US
dc.subjectBiology, Microbiology.en_US
dc.subjectHealth Sciences, Immunology.en_US
dc.titleAntibody-enhanced dengue virus infection of human mast cells.en_US
dc.typetexten_US
dc.contributor.degreePh.D.en_US
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