title: Identification of host genes leading to West Nile virus encephalitis in mice brain using RNA-seq analysis.
abstract: Differential host responses may be critical determinants of distinct pathologies of West Nile virus (WNV) NY99 (pathogenic) and WNV Eg101 (non-pathogenic) strains. We employed RNA-seq technology to analyze global differential gene expression in WNV-infected mice brain and to identify the host cellular factors leading to lethal encephalitis. We identified 1,400 and 278 transcripts, which were differentially expressed after WNV NY99 and WNV Eg101 infections, respectively, and 147 genes were common to infection with both the viruses. Genes that were up-regulated in infection with both the viruses were mainly associated with interferon signaling. Genes associated with inflammation and cell death/apoptosis were only expressed after WNV NY99 infection. We demonstrate that differences in the activation of key pattern recognition receptors resulted in the induction of unique innate immune profiles, which corresponded with the induction of interferon and inflammatory responses. Pathway analysis of differentially expressed genes indicated that after WNV NY99 infection, TREM-1 mediated activation of toll-like receptors leads to the high inflammatory response. In conclusion, we have identified both common and specific responses to WNV NY99 and WNV Eg101 infections as well as genes linked to potential resistance to infection that may be targets for therapeutics.
authors.affiliation: Department of Tropical Medicine, Medical Microbiology and Pharmacology, Honolulu, USA.|Pacific Center for Emerging Infectious Diseases Research, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, Hawaii 96813, USA.
authors.forename: Mukesh
authors.initials: M
authors.lastname: Kumar
authors.affiliation: Pacific Center for Emerging Infectious Diseases Research, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, Hawaii 96813, USA.
authors.forename: Mahdi
authors.initials: M
authors.lastname: Belcaid
authors.affiliation: Department of Tropical Medicine, Medical Microbiology and Pharmacology, Honolulu, USA.|Pacific Center for Emerging Infectious Diseases Research, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, Hawaii 96813, USA.
authors.forename: Vivek R
authors.initials: VR
authors.lastname: Nerurkar
mesh_terms: D000818:Animals; D001921:Brain / Q000821:virology*; D004195:Disease Models, Animal; D004351:Drug Resistance; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D051379:Mice; D017423:Sequence Analysis, RNA / Q000379:methods*; D014901:West Nile Fever / Q000235:genetics*; D014902:West Nile virus / Q000145:classification / Q000472:pathogenicity*