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Clin Vaccine Immunol. 2015 Jan;22(1):6-16. doi: 10.1128/CVI.00508-14. Epub 2014 Oct 29.

Systems immunology reveals markers of susceptibility to West Nile virus infection.

Author information

1
Section of Rheumatology, Yale School of Medicine, New Haven, Connecticut, USA.
2
Center for Computational and Integrative Biology, Massachusetts General Hospital, Boston, Massachusetts, USA.
3
Interdepartmental Program in Computational Biology and Bioinformatics, Yale School of Medicine, New Haven, Connecticut, USA.
4
Section of Infectious Disease, Yale School of Medicine, New Haven, Connecticut, USA.
5
Department of Laboratory Medicine, Yale School of Medicine, New Haven, Connecticut, USA.
6
Department of Neurology, Yale School of Medicine, New Haven, Connecticut, USA.
7
Baylor College of Medicine, Houston, Texas, USA.
8
Department of Immunology, Rappaport Institute of Medical Research, Faculty of Medicine and Faculty of Biology, Technion, Haifa, Israel.
9
Section of Infectious Disease, Yale School of Medicine, New Haven, Connecticut, USA Howard Hughes Medical Institute, Yale School of Medicine, New Haven, Connecticut, USA.
10
Interdepartmental Program in Computational Biology and Bioinformatics, Yale School of Medicine, New Haven, Connecticut, USA Department of Pathology, Yale School of Medicine, New Haven, Connecticut, USA.
11
Section of Rheumatology, Yale School of Medicine, New Haven, Connecticut, USA ruth.montgomery@yale.edu.

Abstract

West Nile virus (WNV) infection is usually asymptomatic but can cause severe neurological disease and death, particularly in older patients, and how individual variations in immunity contribute to disease severity is not yet defined. Animal studies identified a role for several immunity-related genes that determine the severity of infection. We have integrated systems-level transcriptional and functional data sets from stratified cohorts of subjects with a history of WNV infection to define whether these markers can distinguish susceptibility in a human population. Transcriptional profiles combined with immunophenotyping of primary cells identified a predictive signature of susceptibility that was detectable years after acute infection (67% accuracy), with the most prominent alteration being decreased IL1B induction following ex vivo infection of macrophages with WNV. Deconvolution analysis also determined a significant role for CXCL10 expression in myeloid dendritic cells. This systems analysis identified markers of pathogenic mechanisms and offers insights into potential therapeutic strategies.

PMID:
25355795
PMCID:
PMC4278927
DOI:
10.1128/CVI.00508-14
[Indexed for MEDLINE]
Free PMC Article
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