title: Identification of genes critical for resistance to infection by West Nile virus using RNA-Seq analysis.
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.
authors.affiliation: Section of Rheumatology, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Feng
authors.initials: F
authors.lastname: Qian
authors.forename: Lisa
authors.initials: L
authors.lastname: Chung
authors.forename: Wei
authors.initials: W
authors.lastname: Zheng
authors.forename: Vincent
authors.initials: V
authors.lastname: Bruno
authors.forename: Roger P
authors.initials: RP
authors.lastname: Alexander
authors.forename: Zhong
authors.initials: Z
authors.lastname: Wang
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Wang
authors.forename: Sebastian
authors.initials: S
authors.lastname: Kurscheid
authors.forename: Hongyu
authors.initials: H
authors.lastname: Zhao
authors.forename: Erol
authors.initials: E
authors.lastname: Fikrig
authors.forename: Mark
authors.initials: M
authors.lastname: Gerstein
authors.forename: Michael
authors.initials: M
authors.lastname: Snyder
authors.forename: Ruth R
authors.initials: RR
authors.lastname: Montgomery
mesh_terms: D000328:Adult; D060467:Disease Resistance / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D055785:Gene Knockdown Techniques; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008264:Macrophages / Q000276:immunology* / Q000821:virology*; D008297:Male; D012313:RNA / Q000096:biosynthesis* / Q000235:genetics*; D014902:West Nile virus / Q000276:immunology*; D055815:Young Adult
chemical_list: D012313:RNA