Waickman Adam T, Friberg Heather, Gromowski Gregory D, Rutvisuttinunt Wiriya, Li Tao, Siegfried Hayden, Victor Kaitlin, McCracken Michael K, Fernandez Stefan, Srikiatkhachorn Anon, Ellison Damon, Jarman Richard G, Thomas Stephen J, Rothman Alan L, Endy Timothy, Currier Jeffrey R
Viral Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, Maryland, United States of America.
Institute for Global Health and Translational Sciences, State University of New York Upstate Medical University, Syracuse, New York, United States of America.
PLoS Pathog. 2021 Jan 29;17(1):e1009240. doi: 10.1371/journal.ppat.1009240. eCollection 2021 Jan.
Dengue human infection studies present an opportunity to address many longstanding questions in the field of flavivirus biology. However, limited data are available on how the immunological and transcriptional response elicited by an attenuated challenge virus compares to that associated with a wild-type DENV infection. To determine the kinetic transcriptional signature associated with experimental primary DENV-1 infection and to assess how closely this profile correlates with the transcriptional signature accompanying natural primary DENV-1 infection, we utilized scRNAseq to analyze PBMC from individuals enrolled in a DENV-1 human challenge study and from individuals experiencing a natural primary DENV-1 infection. While both experimental and natural primary DENV-1 infection resulted in overlapping patterns of inflammatory gene upregulation, natural primary DENV-1 infection was accompanied with a more pronounced suppression in gene products associated with protein translation and mitochondrial function, principally in monocytes. This suggests that the immune response elicited by experimental and natural primary DENV infection are similar, but that natural primary DENV-1 infection has a more pronounced impact on basic cellular processes to induce a multi-layered anti-viral state.
登革热人类感染研究为解决黄病毒生物学领域许多长期存在的问题提供了契机。然而，关于减毒攻毒病毒引发的免疫和转录反应与野生型登革病毒感染相关反应相比的数据有限。为了确定与实验性原发性登革病毒1型感染相关的动态转录特征，并评估该特征与自然原发性登革病毒1型感染伴随的转录特征的相关性，我们利用单细胞RNA测序分析了参与登革病毒1型人类攻毒研究的个体以及经历自然原发性登革病毒1型感染的个体的外周血单核细胞。虽然实验性和自然原发性登革病毒1型感染均导致炎症基因上调的重叠模式，但自然原发性登革病毒1型感染伴随着与蛋白质翻译和线粒体功能相关的基因产物更明显的抑制，主要发生在单核细胞中。这表明实验性和自然原发性登革病毒感染引发的免疫反应相似，但自然原发性登革病毒1型感染对基本细胞过程有更明显的影响，以诱导多层次的抗病毒状态。
