%0 Journal Article
%T Roles for Endothelial Cells in Dengue Virus Infection
%A Nadine A. Dalrymple
%A Erich R. Mackow
%J Advances in Virology
%D 2012
%I Hindawi Publishing Corporation
%R 10.1155/2012/840654
%X Dengue viruses cause two severe diseases that alter vascular fluid barrier functions, dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). The endothelium is the primary fluid barrier of the vasculature and ultimately the effects of dengue virus infection that cause capillary leakage impact endothelial cell (EC) barrier functions. The ability of dengue virus to infect the endothelium provides a direct means for dengue to alter capillary permeability, permit virus replication, and induce responses that recruit immune cells to the endothelium. Recent studies focused on dengue virus infection of primary ECs have demonstrated that ECs are efficiently infected, rapidly produce viral progeny, and elicit immune enhancing cytokine responses that may contribute to pathogenesis. Furthermore, infected ECs have also been implicated in enhancing viremia and immunopathogenesis within murine dengue disease models. Thus dengue-infected ECs have the potential to directly contribute to immune enhancement, capillary permeability, viremia, and immune targeting of the endothelium. These effects implicate responses of the infected endothelium in dengue pathogenesis and rationalize therapeutic targeting of the endothelium and EC responses as a means of reducing the severity of dengue virus disease. 1. Introduction Dengue viruses are transmitted by mosquitoes and infect ‵ 50 million people annually with an additional 2.5 billion people at risk living in tropical areas [1每3]. Expanding mosquito habitats are increasing the range of dengue virus outbreaks and the occurrence of severe diseases with 5每30% mortality rates: dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) [1每3]. The majority of patients are asymptomatic or display mild symptoms of dengue fever (DF) which include rapid onset of fever, viremia, headache, pain, and rash [4]. Patients with DHF and DSS display symptoms of DF in addition to increased edema, hemorrhage, thrombocytopenia, and shock [1每3]. Although patient progression to DHF and DSS is not fully understood [3, 5], antibody-dependent enhancement (ADE) of dengue infection increases the potential for DSS and DHF [3, 6, 7]. There are four dengue virus serotypes (types 1每4) and infection by one serotype predisposes individuals to more severe disease following a subsequent infection by a different dengue serotype. The circulation of serotype-specific cross-reactive antibodies or preexisting maternal antibodies may contribute to progression to DHF/DSS by facilitating viral infection of immune cells and eliciting cytokine and chemotactic
%U http://www.hindawi.com/journals/av/2012/840654/