Pathogenesis and Inhibition of Flaviviruses from a Carbohydrate Perspective.
Pathogenesis and Inhibition of Flaviviruses from a Carbohydrate Perspective.
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DOI：
10.3390/ph10020044
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发表时间：
2017-05-04
期刊：
影响因子：
--
通讯作者：
Linhardt RJ
中科院分区：
文献类型：
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作者：
Kim SY;Li B;Linhardt RJ
黄病毒是一种有包膜的阳性单链核糖核酸（RNA）病毒，具有多种传播途径。虽然致病性黄病毒引起的症状的类型和严重程度从出血热到胎儿畸形不等，但它们进入宿主细胞的一般机制是相似的。所有致病性黄病毒，如登革热病毒、黄热病病毒、西尼罗河病毒、日本脑炎病毒和寨卡病毒，通过其包膜蛋白内的推定GAG结合位点与糖胺聚糖（GAG）结合以进入宿主细胞表面。GAG是具有重复二糖单元的长的线性阴离子多糖，并且参与许多生物过程，例如细胞信号传导、细胞粘附和发病机制。黄病毒囊膜蛋白是一种N-糖基化的表面蛋白，通过其聚糖与C-型凝集素、树突状细胞特异性细胞间粘附分子-3-抓取非整合素（DC-SIGN）相互作用。在这篇综述中，我们讨论了宿主和病毒的表面受体，具有碳水化合物成分，重点是在黄病毒进入的早期阶段的表面相互作用。详细讨论了GAG-黄病毒包膜蛋白的相互作用以及黄病毒包膜蛋白和DC-SIGN之间的相互作用。这篇评论还探讨了天然和合成的抑制剂的黄病毒是碳水化合物为基础的或碳水化合物为目标。这些抑制剂的优点和缺点进行了探讨，是潜在的策略，以提高其疗效，最终帮助根除黄病毒感染。
Flaviviruses are enveloped, positive single stranded ribonucleic acid (RNA) viruses with various routes of transmission. While the type and severity of symptoms caused by pathogenic flaviviruses vary from hemorrhagic fever to fetal abnormalities, their general mechanism of host cell entry is similar. All pathogenic flaviviruses, such as dengue virus, yellow fever virus, West Nile virus, Japanese encephalitis virus, and Zika virus, bind to glycosaminglycans (GAGs) through the putative GAG binding sites within their envelope proteins to gain access to the surface of host cells. GAGs are long, linear, anionic polysaccharides with a repeating disaccharide unit and are involved in many biological processes, such as cellular signaling, cell adhesion, and pathogenesis. Flavivirus envelope proteins are N-glycosylated surface proteins, which interact with C-type lectins, dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) through their glycans. In this review, we discuss both host and viral surface receptors that have the carbohydrate components, focusing on the surface interactions in the early stage of flavivirus entry. GAG-flavivirus envelope protein interactions as well as interactions between flavivirus envelope proteins and DC-SIGN are discussed in detail. This review also examines natural and synthetic inhibitors of flaviviruses that are carbohydrate-based or carbohydrate-targeting. Both advantages and drawbacks of these inhibitors are explored, as are potential strategies to improve their efficacy to ultimately help eradicate flavivirus infections.