title: Integrated analysis of microRNAs and their disease related targets in the brain of mice infected with West Nile virus.
abstract: To determine whether cellular miRNAs play a role in West Nile virus (WNV) neuropathogenesis, we evaluated WNV-infected mice brain for the expression profile of miRNAs, their potential functions and their correlation with genes involved in inflammatory pathways. A total of 528 miRNAs and 168 mRNA genes were examined. One hundred thirty-nine miRNAs were significantly differentially expressed in WNV-infected mice brain. Ingenuity pathway analysis demonstrated that these miRNAs and their target genes are involved in pathways related to inflammatory response, immune-cell trafficking and cell death. Moreover, we demonstrate an inverse correlation between WNV-modulated miRNAs and their target neuroinflammatory genes in the same mice brain. We demonstrate that miR-196a, miR-202-3p, miR-449c, and miR-125a-3p target multiple genes involving cytokines, chemokines, and apoptotic genes, which belong to different signaling pathways that play critical role in WNV neuropathogenesis. Functional studies targeting specific miRNA are warranted to develop therapeutics for the management of WNV disease.
authors.affiliation: Department of Tropical Medicine, Medical Microbiology and Pharmacology, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, HI 96813, USA; Pacific Center for Emerging Infectious Diseases Research, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, HI 96813, USA.
authors.forename: Mukesh
authors.initials: M
authors.lastname: Kumar
authors.affiliation: Department of Tropical Medicine, Medical Microbiology and Pharmacology, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, HI 96813, USA; Pacific Center for Emerging Infectious Diseases Research, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, HI 96813, USA. Electronic address: nerurkar@hawaii.edu.
authors.forename: Vivek R
authors.initials: VR
authors.lastname: Nerurkar
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism / Q000821:virology*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D014901:West Nile Fever / Q000235:genetics* / Q000378:metabolism / Q000821:virology; D014902:West Nile virus / Q000502:physiology*
chemical_list: D016207:Cytokines; D035683:MicroRNAs
keywords: Flavivirus; Neuroinflammation; PCR array; West Nile virus; miR-125a-3p; miR-196a; miR-202-3p; miR-449c; miRNA