Abstract | UNLABELLED:
MicroRNAs ( miRNAs) are single-stranded small RNA molecules that regulate various cellular processes. miRNA 155 (miR-155) regulates various aspects of innate and adaptive immune responses and plays a key role in various viral infections and the resulting neuroinflammation. The present study evaluated the involvement of miR-155 in modulating Japanese encephalitis virus (JEV)-induced neuroinflammation. We observed that miR-155 expression was upregulated during JEV infection of mouse primary microglia, the BV-2 microglia cell line, and in both mouse and human brains. In vitro and in vivo knockdown of miR-155 minimized JEV-induced inflammatory responses. In the present study, we confirmed targeting of the Src homology 2-containing inositol phosphatase 1 (SHIP1) 3' untranslated region (UTR) by miR-155 in the context of JEV infection. Inhibition of SHIP1 by miR-155 resulted in higher beta interferon (IFN-β) and proinflammatory cytokine production through activation of TANK-binding kinase 1 (TBK-1). Based on these observations, we conclude that miR-155 modulates the neuroinflammatory response during JEV infection via negative regulation of SHIP1 expression. Thus, modulation of miR-155 could be a novel strategy to regulate JEV-induced neuroinflammation. IMPORTANCE:
|
Authors | Menaka Chanu Thounaojam, Kiran Kundu, Deepak Kumar Kaushik, Shalini Swaroop, Anita Mahadevan, Susarla Krishna Shankar, Anirban Basu |
Journal | Journal of virology
(J Virol)
Vol. 88
Issue 9
Pg. 4798-810
(May 2014)
ISSN: 1098-5514 [Electronic] United States |
PMID | 24522920
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Chemical References |
- MIRN155 microRNA, human
- MicroRNAs
- Mirn155 microRNA, mouse
- Phosphoric Monoester Hydrolases
- Inositol Polyphosphate 5-Phosphatases
- INPP5D protein, human
- Inpp5d protein, mouse
- Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases
|
Topics |
- Animals
- Brain
(pathology)
- Cells, Cultured
- Disease Models, Animal
- Encephalitis Virus, Japanese
(immunology)
- Encephalitis, Japanese
(immunology, pathology)
- Gene Expression Profiling
- Gene Knockdown Techniques
- Host-Pathogen Interactions
- Humans
- Inositol Polyphosphate 5-Phosphatases
- Mice
- Mice, Inbred BALB C
- MicroRNAs
(metabolism)
- Microglia
(immunology)
- Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases
- Phosphoric Monoester Hydrolases
(biosynthesis)
|