Early cellular and molecular signatures correlate with severity of West Nile virus infection
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1-s2.0-S2589004223024641-main.pdf
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Published version
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5.5 MB
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Author(s) • • • • • • • • •
Lee, Ho-Joon
Zhao, Yujiao
Fleming, Ira
Mehta, Sameet
Wang, Xiaomei
Wyk, Brent Vander
Ronca, Shannon E
Kang, Heather
Chou, Chih-Hung
Fatou, Benoit
Date Issued
December 15, 2023
Journal
iScience
Publisher
Elsevier BV
Citation
Lee, Ho-Joon, Zhao, Yujiao, Fleming, Ira, Mehta, Sameet, Wang, Xiaomei et al. 2023. "Early cellular and molecular signatures correlate with severity of West Nile virus infection." iScience, 26 (12).
Version
Final published version
Abstract
Infection with West Nile virus (WNV) drives a wide range of responses, from asymptomatic to flu-like symptoms/fever or severe cases of encephalitis and death. To identify cellular and molecular signatures distinguishing WNV severity, we employed systems profiling of peripheral blood from asymptomatic and severely ill individuals infected with WNV. We interrogated immune responses longitudinally from acute infection through convalescence employing single-cell protein and transcriptional profiling complemented with matched serum proteomics and metabolomics as well as multi-omics analysis. At the acute time point, we detected both elevation of pro-inflammatory markers in innate immune cell types and reduction of regulatory T cell activity in participants with severe infection, whereas asymptomatic donors had higher expression of genes associated with anti-inflammatory CD16+ monocytes. Therefore, we demonstrated the potential of systems immunology using multiple cell-type and cell-state-specific analyses to identify correlates of infection severity and host cellular activity contributing to an effective anti-viral response.
MIT Department
Institute for Medical Engineering and Science
Massachusetts Institute of Technology. Department of Chemistry
Koch Institute for Integrative Cancer Research at MIT
Broad Institute of MIT and Harvard
Ragon Institute of MGH, MIT and Harvard
Klarman Cell Observatory (Broad Institute)
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Creative Commons Attribution-NonCommercial-NoDerivatives
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DOI of Published Version
https://doi.org/10.1016/j.isci.2023.108387