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Virology. 2014 Mar;452-453:143-51. doi: 10.1016/j.virol.2014.01.004. Epub 2014 Jan 31.

Integrated analysis of microRNAs and their disease related targets in the brain of mice infected with West Nile virus.

Author information

1
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.
2
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.

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.

KEYWORDS:

Flavivirus; Neuroinflammation; PCR array; West Nile virus; miR-125a-3p; miR-196a; miR-202-3p; miR-449c; miRNA

PMID:
24606691
PMCID:
PMC3959158
DOI:
10.1016/j.virol.2014.01.004
[Indexed for MEDLINE]
Free PMC Article
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