| Nederlands

Cell entry mechanisms of dengue virus

(2009) Schaar, Hilde Margot van der

Dengue virus (DENV) currently causes the most common mosquito-borne viral infection worldwide. According to the estimates of the World Health Organization, 50 to 100 million infections occur annually leading to 500,000 hospitalizations and 20,000 deaths. Despite this high impact, there are neither vaccines nor antiviral drugs available to prevent or treat DENV infections. DENV can cause disease in humans ranging from dengue fever, an illness with flu-like symptoms, to the more severe dengue hemorrhagic fever, characterized by potentially life-threatening bleeding manifestions. Antibodies are believed to play an important role in controlling disease severity by directly influencing the infectious properties of the virus. The studies presented in this thesis elucidate the mechanisms that DENV uses to enter and infect the host cell. First, we have followed individual fluorescently labeled virus particles in real-time as they enter a cell, in which different compartments are illuminated by fluorescent marker proteins. Thus, we have visualized the cell entry pathway of DENV and identified the organelle in which the virus undergoes membrane fusion to deliver its genome into the cell. Additionally, we have investigated the infectious properties of a subpopulation of DENV particles, called immature particles, that are considered to be non-infectious. Remarkably, with the help of antibodies, immature DENV particles are able to productively infect cells and therefore might participate in the pathogenesis of severe disease. Collectively, our findings have enriched our knowledge on the critical determinants in DENV infection and may contribute to the development of antiviral drugs and safe dengue vaccines.

	Title and contents
	Chapter 1
	Chapter 2
	Chapter 3
	Chapter 4
	Chapter 5
	Summarizing discussion
	Samenvatting
	Dankwoord
	Contributing authors
	Abbreviations
	Complete thesis