Hamlin Rebecca E, Rahman Adeeb, Pak Theodore R, Maringer Kevin, Mena Ignacio, Bernal-Rubio Dabeiba, Potla Uma, Maestre Ana M, Fredericks Anthony C, Amir El-Ad D, Kasarskis Andrew, Ramos Irene, Merad Miriam, Fernandez-Sesma Ana
Department of Microbiology.
Graduate School of Biomedical Sciences.
JCI Insight. 2017 Jul 6;2(13). doi: 10.1172/jci.insight.92424.
Dengue virus (DENV) is the most prevalent mosquito-borne virus causing human disease. Of the 4 DENV serotypes, epidemiological data suggest that DENV-2 secondary infections are associated with more severe disease than DENV-4 infections. Mass cytometry by time-of-flight (CyTOF) was used to dissect immune changes induced by DENV-2 and DENV-4 in human DCs, the initial targets of primary infections that likely affect infection outcomes. Strikingly, DENV-4 replication peaked earlier and promoted stronger innate immune responses, with increased expression of DC activation and migration markers and increased cytokine production, compared with DENV-2. In addition, infected DCs produced higher levels of inflammatory cytokines compared with bystander DCs, which mainly produced IFN-induced cytokines. These high-dimensional analyses during DENV-2 and DENV-4 infections revealed distinct viral signatures marked by different replication strategies and antiviral innate immune induction in DCs, which may result in different viral fitness, transmission, and pathogenesis.
登革病毒（DENV）是导致人类疾病的最常见蚊媒病毒。在4种登革病毒血清型中，流行病学数据表明，与DENV-4感染相比，DENV-2二次感染与更严重的疾病相关。采用飞行时间质谱流式细胞术（CyTOF）剖析DENV-2和DENV-4在人树突状细胞（DC）中诱导的免疫变化，DC是初次感染的初始靶点，可能影响感染结果。令人惊讶的是，与DENV-2相比，DENV-4复制峰值出现得更早，并促进更强的先天免疫反应，DC激活和迁移标志物的表达增加，细胞因子产生增加。此外，与旁观者DC相比，感染的DC产生更高水平的炎性细胞因子，旁观者DC主要产生IFN诱导的细胞因子。在DENV-2和DENV-4感染期间的这些高维分析揭示了不同的病毒特征，其特征是DC中不同的复制策略和抗病毒先天免疫诱导，这可能导致不同的病毒适应性、传播和发病机制。
