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 PMID:30150281  

Comprehensive innate immune profiling of chikungunya virus infection in pediatric cases.

Daniela Michlmayr | Theodore R Pak | Adeeb H Rahman | El-Ad David Amir | Eun-Young Kim | Seunghee Kim-Schulze | Maria Suprun | Michael G Stewart | Guajira P Thomas | Angel Balmaseda | Li Wang | Jun Zhu | Mayte Suaréz-Fariñas | Steven M Wolinsky | Andrew Kasarskis | Eva Harris
Molecular systems biology | 2018

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.

Pubmed ID: 30150281

Associated grants

  • Agency: NIAID NIH HHS, United States
    Id: F30 AI122673
  • Agency: NIAID NIH HHS, United States
    Id: R33 AI100186
  • Agency: NIH HHS, United States
    Id: S10 OD018522
  • Agency: NIAID NIH HHS, United States
    Id: U19 AI118610

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FASTX-Toolkit (tool)

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Quality control software that perform checks on raw sequence data coming from high throughput sequencing pipelines. This software also provides a modular set of analyses which can give a quick impression of the quality of the data prior to further analysis.

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RRID:SCR_001575

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