Systems Immunology Reveals Markers of Susceptibility to West Nile Virus Infection

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 gene...

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Published inClinical and vaccine immunology Vol. 22; no. 1; pp. 6 - 16
Main Authors Qian, Feng, Goel, Gautam, Meng, Hailong, Wang, Xiaomei, You, Fuping, Devine, Lesley, Raddassi, Khadir, Garcia, Melissa N., Murray, Kristy O., Bolen, Christopher R., Gaujoux, Renaud, Shen-Orr, Shai S., Hafler, David, Fikrig, Erol, Xavier, Ramnik, Kleinstein, Steven H., Montgomery, Ruth R.
Format Journal Article
LanguageEnglish
Published United States American Society for Microbiology 01.01.2015
Subjects
Adult
Aged
Aged, 80 and over
Chemokine CXCL10 - biosynthesis
Chemokine CXCL10 - immunology
Clinical Immunology
Disease Susceptibility
Female
Gene Expression Profiling
Genetic Markers
Humans
Immunophenotyping
Interleukin-1beta - biosynthesis
Interleukin-1beta - immunology
Male
Middle Aged
Systems Biology - methods
Transcription, Genetic
West Nile virus
West Nile virus - immunology
Young Adult
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Summary: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.
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F.Q., G.G., and H.M. contributed equally to this work. S.H.K. and R.R.M. contributed equally to this work.
Present address: Feng Qian, State Key Laboratory of Genetic Engineering and Ministry of Education Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, China; Christopher R. Bolen, Stanford University, Beckman Center, Stanford, California, USA.
Citation Qian F, Goel G, Meng H, Wang X, You F, Devine L, Raddassi K, Garcia MN, Murray KO, Bolen CR, Gaujoux R, Shen-Orr SS, Hafler D, Fikrig E, Xavier R, Kleinstein SH, Montgomery RR. 2015. Systems immunology reveals markers of susceptibility to West Nile virus infection. Clin Vaccine Immunol 22:6–16. doi:10.1128/CVI.00508-14.
ISSN:1556-6811
1556-679X
1556-679X
DOI:10.1128/CVI.00508-14