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- Title
Comprehensive innate immune profiling of chikungunya virus infection in pediatric cases.
- Authors
Michlmayr, Daniela; Pak, Theodore R; Rahman, Adeeb H; Amir, El-Ad David; Kim, Eun-Young; Kim-Schulze, Seunghee; Suprun, Maria; Stewart, Michael G; Thomas, Guajira P; Balmaseda, Angel; Wang, Li; Zhu, Jun; Suaréz-Fariñas, Mayte; Wolinsky, Steven M; Kasarskis, Andrew; Harris, Eva
- Abstract
Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that causes global epidemics of debilitating disease worldwide. To gain functional insight into the host cellular genes required for virus infection, we performed whole-blood RNA-seq, 37-plex mass cytometry of peripheral blood mononuclear cells (PBMCs), and serum cytokine measurements of acute- and convalescent-phase samples obtained from 42 children naturally infected with CHIKV. Semi-supervised classification and clustering of single-cell events into 57 sub-communities of canonical leukocyte phenotypes revealed a monocyte-driven response to acute infection, with the greatest expansions in “intermediate” CD14++CD16+ monocytes and an activated subpopulation of CD14+ monocytes. Increases in acute-phase CHIKV envelope protein E2 expression were highest for monocytes and dendritic cells. Serum cytokine measurements confirmed significant acute-phase upregulation of monocyte chemoattractants. Distinct transcriptomic signatures were associated with infection timepoint, as well as convalescent-phase anti- CHIKV antibody titer, acute-phase viremia, and symptom severity. We present a multiscale network that summarizes all observed modulations across cellular and transcriptomic levels and their interactions with clinical outcomes, providing a uniquely global view of the biomolecular landscape of human CHIKV infection.
- Publication
Molecular Systems Biology, 2018, Vol 14, Issue 8, p1
- ISSN
1744-4292
- Publication type
Article
- DOI
10.15252/msb.20177862