Early Cellular and Molecular Signatures Correlate With Severity of West Nile Virus Infection

Authors

Ho-Joon Lee
Yujiao Zhao
Ira Fleming
Sameet Mehta
Xiaomei Wang
Brent Vander Wyk
Shannon E Ronca
Heather Kang
Chih-Hung Chou
Benoit Fatou
Kinga K Smolen
Ofer Levy
Clary B Clish
Ramnik J Xavier
Hanno Steen
David A Hafler
J Christopher Love
Alex K Shalek
Leying Guan
Kristy O Murray
Steven H Kleinstein
Ruth R Montgomery

Publication Date

12-15-2023

Journal

iScience

DOI

10.1016/j.isci.2023.108387

PMID

38047068

PMCID

PMC10692672

PubMedCentral® Posted Date

11-2-2023

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

Virology, Diagnostics

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