Open AccessArticle
Identification of Genes Critical for Resistance to Infection by West Nile Virus Using RNA-Seq Analysis
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Feng Qian 1, Lisa Chung 2,3, Wei Zheng 2, Vincent Bruno 4,†, Roger P. Alexander 4,5, Zhong Wang 4,‡, Xiaomei Wang 1, Sebastian Kurscheid 6, Hongyu Zhao 2,3, Erol Fikrig 6,7, Mark Gerstein 4,5,8, Michael Snyder 9 and Ruth R. Montgomery 1,*
1
Section of Rheumatology, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA
2
Keck Biotechnology Resource Laboratory, Yale University School of Medicine, New Haven, CT 06520, USA
3
Department of Biostatistics, Yale University School of Medicine, New Haven, CT 06520, USA
4
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA
5
Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT 06520, USA
6
Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA
7
The Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA
8
Department of Computer Science, Yale University, New Haven, CT 06520, USA
9
Department of Genetics, Stanford University, Stanford, CA 94305, USA
†
Current address: Department of Microbiology and Immunology, Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
‡
Current address: DOE Joint Genome Institute, 2800 Mitchell Dr., MS100, Walnut Creek, CA 94598, USA.
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Abstract
The West Nile virus (WNV) is an emerging infection of biodefense concern and there are no available treatments or vaccines. Here we used a high-throughput method based on a novel gene expression analysis, RNA-Seq, to give a global picture of differential gene expression
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The West Nile virus (WNV) is an emerging infection of biodefense concern and there are no available treatments or vaccines. Here we used a high-throughput method based on a novel gene expression analysis, RNA-Seq, to give a global picture of differential gene expression by primary human macrophages of 10 healthy donors infected
in vitro with WNV. From a total of 28 million reads per sample, we identified 1,514 transcripts that were differentially expressed after infection. Both predicted and novel gene changes were detected, as were gene isoforms, and while many of the genes were expressed by all donors, some were unique. Knock-down of genes not previously known to be associated with WNV resistance identified their critical role in control of viral infection. Our study distinguishes both common gene pathways as well as novel cellular responses. Such analyses will be valuable for translational studies of susceptible and resistant individuals—and for targeting therapeutics—in multiple biological settings.
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