Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, United States.
Front Cell Infect Microbiol. 2020 Sep 10;10:489. doi: 10.3389/fcimb.2020.00489. eCollection 2020.
Dengue is an acute febrile disease triggered by dengue virus. Dengue is the widespread and rapidly transmitted mosquito-borne viral disease of humans. Diverse symptoms and diseases due to Dengue virus (DENV) infection ranges from dengue fever, dengue hemorrhagic fever (life-threatening) and dengue shock syndrome characterized by shock, endothelial dysfunction and vascular leakage. Several studies have linked the severity of dengue with the induction of inflammasome. DENV activates the NLRP3-specific inflammasome in DENV infected human patients, mice; specifically, mouse bone marrow derived macrophages (BMDMs), dendritic cells, endothelial cells, human peripheral blood mononuclear cells (PBMCs), keratinocytes, monocyte-differentiated macrophages (THP-1), and platelets. Dengue virus mediated inflammasome initiates the maturation of IL-1β and IL-18, which are critical for dengue pathology and inflammatory response. Several studies have reported the molecular mechanism through which (host and viral factors) dengue induces inflammasome, unravels the possible mechanisms of DENV pathogenesis and sets up the stage for the advancement of DENV therapeutics. In this perspective article, we discuss the potential implications and our understanding of inflammasome mechanisms of dengue virus and highlight research areas that have potential to inhibit the pathogenesis of viral diseases, specifically for dengue.
登革热是由登革病毒引起的急性发热性疾病。登革热是一种广泛传播且传播迅速的蚊媒病毒性疾病,人类易患该病。登革病毒(DENV)感染引起的多种症状和疾病包括登革热、登革出血热(危及生命)和登革休克综合征,其特征为休克、内皮功能障碍和血管渗漏。多项研究表明,登革热的严重程度与炎症小体的诱导有关。DENV 在感染 DENV 的人类患者、小鼠中激活 NLRP3 特异性炎症小体;具体而言,激活小鼠骨髓来源的巨噬细胞(BMDM)、树突状细胞、内皮细胞、人外周血单核细胞(PBMC)、角质形成细胞、单核细胞分化的巨噬细胞(THP-1)和血小板。登革病毒介导的炎症小体启动 IL-1β 和 IL-18 的成熟,这对于登革热病理学和炎症反应至关重要。多项研究报告了登革热诱导炎症小体的分子机制,揭示了 DENV 发病机制的可能机制,并为 DENV 治疗的进展奠定了基础。在这篇观点文章中,我们讨论了炎症小体机制在登革热病毒中的潜在意义和我们的理解,并强调了具有抑制病毒疾病发病机制潜力的研究领域,特别是针对登革热。