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Hazra, B and Kumawat, KL and Basu, A (2017) The host microRNA miR-301a blocks the IRF1-mediated neuronal innate immune response to Japanese encephalitis virus infection. SCIENCE SIGNALING, 10 (466).

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3. The host microRNA miR-301a blocks the IRF1 mediated neuronal.pdf
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Abstract

Effective recognition of viral components and the subsequent stimulation of the production of type I interferons (IFNs) is crucial for the induction of host antiviral immunity. The failure of the host to efficiently produce type I IFNs in response to infection by the Japanese encephalitis virus (JEV) is linked with an increased probability for the disease to become lethal. JEV is a neurotropic virus of the Flaviviridae family that causes encephalitis in humans. JEV infection is regulated by several host factors, including microRNAs, which are conserved noncoding RNAs that participate in various physiological and pathological processes. We showed that the JEV-induced expression of miR-301a led to inhibition of the production of type I IFN by reducing the abundances of the transcription factor IFN regulatory factor 1 (IRF1) and the signaling protein suppressor of cytokine signaling 5 (SOCS5). Mechanistically, induction of miR-301a expression during JEV infection required the transcription factor nuclear factor κB. In mouse neurons, neutralization of miR-301a restored the host innate immune response by enabling IFN-β production, thereby restricting viral propagation. Inhibition of miR-301a in mouse brain rescued the production of IRF1 and SOCS5, increased the generation of IFN-β, and reduced the extent of JEV replication, thus improving mouse survival. Thus, our study suggests that the JEV-induced expression of miR-301a assists viral pathogenesis by suppressing IFN production, which might be targeted by antiviral therapies.

Item Type: Article
Subjects: Neurodegenerative Disorders
Neuro-Oncological Disorders
Neurocognitive Processes
Neuronal Development and Regeneration
Informatics and Imaging
Genetics and Molecular Biology
Depositing User: Dr. D.D. Lal
Date Deposited: 01 Jan 2018 10:37
Last Modified: 18 May 2018 10:27
URI: http://nbrc.sciencecentral.in/id/eprint/291

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