Viruses 2013, 5(7), 1664-1681; doi:10.3390/v5071664
Article

Identification of Genes Critical for Resistance to Infection by West Nile Virus Using RNA-Seq Analysis

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.
* Author to whom correspondence should be addressed.
Received: 8 May 2013; in revised form: 21 June 2013 / Accepted: 29 June 2013 / Published: 8 July 2013
(This article belongs to the Section Animal Viruses)
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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 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.
Keywords: anti-viral gene expression; immune response; macrophage; RNA-Seq; West Nile virus

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MDPI and ACS Style

Qian, F.; Chung, L.; Zheng, W.; Bruno, V.; Alexander, R.P.; Wang, Z.; Wang, X.; Kurscheid, S.; Zhao, H.; Fikrig, E.; Gerstein, M.; Snyder, M.; Montgomery, R.R. Identification of Genes Critical for Resistance to Infection by West Nile Virus Using RNA-Seq Analysis. Viruses 2013, 5, 1664-1681.

AMA Style

Qian F, Chung L, Zheng W, Bruno V, Alexander RP, Wang Z, Wang X, Kurscheid S, Zhao H, Fikrig E, Gerstein M, Snyder M, Montgomery RR. Identification of Genes Critical for Resistance to Infection by West Nile Virus Using RNA-Seq Analysis. Viruses. 2013; 5(7):1664-1681.

Chicago/Turabian Style

Qian, Feng; Chung, Lisa; Zheng, Wei; Bruno, Vincent; Alexander, Roger P.; Wang, Zhong; Wang, Xiaomei; Kurscheid, Sebastian; Zhao, Hongyu; Fikrig, Erol; Gerstein, Mark; Snyder, Michael; Montgomery, Ruth R. 2013. "Identification of Genes Critical for Resistance to Infection by West Nile Virus Using RNA-Seq Analysis." Viruses 5, no. 7: 1664-1681.

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