The Platelet-Virus Interaction: Analysis of Human Platelet Phenotype and Function in the Context of Dengue Virus Exposure 公开
Lane, Crystal Amanda (2010)
Published
Abstract
Dengue is a problematic mosquito-borne disease that is prevalent
in most tropical and sub tropical countries. However, recent
outbreaks in Key West, Florida, and Brazil serves as a vivid
reminder that Dengue is an emerging public health threat to our
continent. One of the hallmark complications in dengue virus
infection is thrombocytopenia, or low platelet count. Dengue virus
can interact directly with platelets, causing activation and
subsequent release of soluble platelet factors. The experiments
presented in this thesis explore the phenotypic and functional
characteristics of human platelets in the context of prolonged
dengue virus exposure in vitro. Specifically, analyses show
that dengue virus exposed platelets display activation-related
characteristics that differed from thrombin induced classical
activation. Further experiments verified the release and function
of biomolecule polyphosphate from dengue virus exposed platelets,
which induced apoptosis in myeloma cells resulting in lower levels
of antibody production. Together, these studies show that dengue
virus exposure causes activation of platelets and subsequent
release of a soluble factor that may be physiologically harmful.
These findings may be important in linking dengue virus associated
thrombocytopenia to the development of dengue pathogenesis in
patients. These investigations also bridge the gap on how platelets
may shape immunity in the course of infection and provide a new
avenue to further understand human immunology during the course of
infection.
Table of Contents
Chapter I: Introduction...1
Introduction...2
A. Overview
1. The dengue virus...3
2. Global burden of dengue disease...4
3. Transmission of dengue virus...4
4. Clinical Features of dengue infection...4
5. Treatment and prevention of dengue virus infection...5
B. Pathophysiology of dengue disease
1. Cellular targets of dengue virus...6
2. Complications of dengue virus infection: DHF...6
Figure Legends...9
Figures 1-2...10
Chapter II: Phenotypic Analysis of Dengue Virus Exposed Platelets...12
Abstract...13
Introduction...14
Material and Methods...16
Results...19
Discussion...21
Figure Legends...23
Figures I-3...25
Chapter III: Functional Analysis of Dengue Virus Exposed Platelets: Secretion of Soluble Mediators...28
Abstract...29
Introduction...30
Material and Methods...32
Results...35
Discussion...37
Figure Legends...39
Figures I-6...42
Chapter IV: Conclusion...48
Concluding Remarks...49
References...50
About this Master's Thesis
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