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

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Author(s): Feng Qian | Lisa Chung | Wei Zheng | Vincent Bruno | Roger P. Alexander | Zhong Wang | Xiaomei Wang | Sebastian Kurscheid | Hongyu Zhao | Erol Fikrig | Mark Gerstein | Michael Snyder | Ruth R. Montgomery

Journal: Viruses
ISSN 1999-4915

Volume: 5;
Issue: 7;
Start page: 1664;
Date: 2013;
Original page

Keywords: anti-viral gene expression | immune response | macrophage | RNA-Seq | West Nile virus

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.

Tango Jona
Tangokurs Rapperswil-Jona

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