The Platelet-Virus Interaction: Analysis of Human Platelet Phenotype and Function in the Context of Dengue Virus Exposure Público

Lane, Crystal Amanda (2010)

Permanent URL: https://etd.library.emory.edu/concern/etds/x059c7949?locale=es
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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

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