Dalrymple Nadine A, Mackow Erich R
Department of Molecular Genetics & Microbiology, Stony Brook University, Stony Brook, NY 11794-5222, USA.
Adv Virol. 2012;2012:840654. doi: 10.1155/2012/840654. Epub 2012 Aug 16.
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.
登革病毒会引发两种严重疾病，即改变血管液体屏障功能的登革出血热（DHF）和登革休克综合征（DSS）。内皮细胞是血管系统的主要液体屏障，登革病毒感染导致毛细血管渗漏的最终影响会冲击内皮细胞（EC）的屏障功能。登革病毒感染内皮细胞的能力为登革病毒改变毛细血管通透性、允许病毒复制以及引发将免疫细胞募集到内皮细胞的反应提供了直接途径。近期针对原代内皮细胞的登革病毒感染研究表明，内皮细胞能被有效感染，迅速产生病毒后代，并引发可能促成发病机制的免疫增强细胞因子反应。此外，在小鼠登革疾病模型中，受感染的内皮细胞也与病毒血症增强和免疫发病机制有关。因此，登革病毒感染的内皮细胞有可能直接促成免疫增强、毛细血管通透性、病毒血症以及内皮细胞的免疫靶向。这些效应表明受感染内皮细胞的反应在登革发病机制中发挥作用，并使以内皮细胞和内皮细胞反应为治疗靶点以降低登革病毒疾病严重程度的做法具有合理性。
