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GSE154386: Temporally integrated single cell RNA sequencing analysis of controlled and natural DENV-1 infections

Bulk RNA sequencing

Controlled dengue human challenge studies present a unique opportunity to address many longstanding questions in the field of flavivirus biology. These fundamental questions include defining the early immunological signatures of infection, the host/environmental factors that impact disease severity, and the role of preexisting immunity on the development of symptomatic viral infection. However, while several controlled dengue human challenge studies have been performed and appear to clinically recapitulate may features of mild natural DENV infection, limited data are available on how the immunological and transcriptional response elicited by these attenuated challenge viruses compares to the profile associated with a natural, unattenuated DENV infection. To bridge this knowledge gap, we performed scRNAseq analysis on longitudinally collected PBMC samples obtained from 3 individuals (8 time points per subject) enrolled in the SUNY/WRAIR DENV-1 controlled human challenge study. In addition, 3 time points (two acute infection time points, one control time point) from two individuals experiencing a natural DENV-1 infection were analyzed and computationally integrated with the challenge model dataset. This temporally integrated dataset contains a total of 171,208 cells and 22 statistically distinct populations corresponding to all major anticipated leukocyte subsets. While all identified cell populations demonstrated significant and consistant perturbations in their transcriptional profile in response to either natural or experimental DENV infection, conventional monocytes respond most robustly to infection across all subjects and study groups from an unbiased transcriptional perspective. Using these data, core sets of genes that were consistently induced by either natural or experimental DENV were identified, and the overlap between the two arms of the study assessed. SOURCE: Adam,Tully,Waickman SUNY Upstate Medical University

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