About this Research Topic
Infection with dengue virus (DENV) can cause severe clinical manifestations resulting in capillary leakage, hemorrhage, and organ impairment that can lead to hypovolemia, shock, and death. DENV is a flavivirus that has emerged in the last several decades as the most significant arboviral infection globally, with up to 96 million symptomatic cases annually in over 100 countries. While most clinical cases of dengue resolve after 1 week, approximately 1-5% of hospitalized patients will develop severe manifestations, during the critical phase (day 4-6 of illness), allowing a window of opportunity to identify patients at risk of progression and potentially intervening with a disease-modifying agent. As yet, no antiviral agents or adjunctive therapies have been found to alter disease outcome in dengue. Novel therapeutics are urgently needed.
The mechanisms underlying the characteristic dengue-associated vasculopathy are likely to be multifactorial, including a variety of host and viral determinants. Endothelial-derived molecules regulate vasomotor tone, cell adhesion, coagulation, inflammation, and permeability. Endothelial cell activation and dysfunction are likely to be involved through various mechanisms. In addition, the endothelial glycocalyx layer, which lines the luminal surface of microvessels and provides vital barrier functions to capillaries, is thought to be involved through viral and NS1 triggered disruption to this layer.
The exact mechanisms associated with the increased capillary permeability, however, are not fully understood. Up to now, lack of an appropriate animal model that mimics human physiology, and the difficulty in studying human endothelial cells in vivo, has hampered research efforts in this area.
This Research Topic welcomes the submission of Original Research Articles, Reviews, Opinion and Perspective articles on the latest discoveries on the pathogenesis of vascular leak in dengue, from basic science and in vitro models through to clinical studies. Emphasis will also be on work investigating or leading to potential dengue disease- and host-directed therapeutics.
The mechanisms underlying the characteristic dengue-associated vasculopathy are likely to be multifactorial, including a variety of host and viral determinants. Endothelial-derived molecules regulate vasomotor tone, cell adhesion, coagulation, inflammation, and permeability. Endothelial cell activation and dysfunction are likely to be involved through various mechanisms. In addition, the endothelial glycocalyx layer, which lines the luminal surface of microvessels and provides vital barrier functions to capillaries, is thought to be involved through viral and NS1 triggered disruption to this layer.
The exact mechanisms associated with the increased capillary permeability, however, are not fully understood. Up to now, lack of an appropriate animal model that mimics human physiology, and the difficulty in studying human endothelial cells in vivo, has hampered research efforts in this area.
This Research Topic welcomes the submission of Original Research Articles, Reviews, Opinion and Perspective articles on the latest discoveries on the pathogenesis of vascular leak in dengue, from basic science and in vitro models through to clinical studies. Emphasis will also be on work investigating or leading to potential dengue disease- and host-directed therapeutics.
Keywords: Dengue, NS1, vasculopathy, endothelium, therapeutics
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