Micro<scp>RNA</scp>‐29b modulates Japanese encephalitis virus‐induced microglia activation by targeting tumor necrosis factor alpha‐induced protein 3

Thounaojam, Menaka C.; Kaushik, Deepak; Kundu, Kiran; Basu, Anirban

doi:10.1111/jnc.12609

Cited by 86 publications

(82 citation statements)

References 51 publications

(121 reference statements)

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“…Thus, in this study, we aimed to address the role of miRNA-regulated pathways in the JEV-induced neuroinflammation model. Recently, the roles of miR-29b and miR-155 in microglial activation during JEV-induced neuroinflammation were studied (42,53,54). In this study, we demonstrated that miR-15b is stimulated both in vitro and in vivo, and miR-15b regulates the inflammatory response following JEV infection by targeting RNF125.…”

Section: Discussionmentioning

confidence: 70%

“…They also reported that miR-29b has a proinflammatory role during JEVinduced microglial activation. They observed nonsignificant changes in viral load after transfection with anti-miR-29b or miR29b mimic compared with JEV alone (54). Additionally, miR-451 knockdown increased IFN-b production and a panel of ISG expression during influenza infection, but it did not impact dendritic cell antiviral capacity (59).…”

Section: Discussionmentioning

confidence: 99%

“…Several studies showed that miRNAs regulate genes related to inflammatory pathways following JEV infection. miR29b is a potent regulator of JEV-induced neuroinflammation by the targeting of TNFAIP3, a negative regulator of NF-kB signaling in microglia cells (54). miR-155 modulates the neuroinflammatory response during JEV infection via negative regulation of SHIP1 expression (42).…”

Section: Discussionmentioning

confidence: 99%

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MicroRNA-15b Modulates Japanese Encephalitis Virus–Mediated Inflammation via Targeting RNF125

Zhu

Nie

et al. 2015

The Journal of Immunology

100

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Japanese encephalitis virus (JEV) can target CNS and cause neuroinflammation that is characterized by profound neuronal damage and concomitant microgliosis/astrogliosis. Although microRNAs (miRNAs) have emerged as a major regulatory network with profound effects on inflammatory response, it is less clear how they regulate JEV-induced inflammation. In this study, we found that miR-15b is involved in modulating the JEV-induced inflammatory response. The data demonstrate that miR-15b is upregulated during JEV infection of glial cells and mouse brains. In vitro overexpression of miR-15b enhances the JEV-induced inflammatory response, whereas inhibition of miR-15b decreases it. Mechanistically, ring finger protein 125 (RNF125), a negative regulator of RIG-I signaling, is identified as a direct target of miR-15b in the context of JEV infection. Furthermore, inhibition of RNF125 by miR-15b results in an elevation in RIG-I levels, which, in turn, leads to a higher production of proinflammatory cytokines and type I IFN. In vivo knockdown of virus-induced miR-15b by antagomir-15b restores the expression of RNF125, reduces the production of inflammatory cytokines, attenuates glial activation and neuronal damage, decreases viral burden in the brain, and improves survival in the mouse model. Taken together, our results indicate that miR-15b modulates the inflammatory response during JEV infection by negative regulation of RNF125 expression. Therefore, miR-15b targeting may constitute an interesting and promising approach to control viral-induced neuroinflammation.

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Section: Discussionmentioning

confidence: 70%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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MicroRNA-15b Modulates Japanese Encephalitis Virus–Mediated Inflammation via Targeting RNF125

Zhu

Nie

et al. 2015

The Journal of Immunology

100

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“…Previously, we showed that miR-29b regulates JEV-induced expression of inducible nitric oxide synthase (iNOS) and COX-2 in BV-2 cells (19). It has previously been reported that miR-155 targets Src homology 2-containing inositol phosphatase 1 (SHIP1) to regulate the inflammatory response (20).…”

mentioning

confidence: 99%

MicroRNA 155 Regulates Japanese Encephalitis Virus-Induced Inflammatory Response by Targeting Src Homology 2-Containing Inositol Phosphatase 1

Thounaojam

Kundu

Kaushik

et al. 2014

J Virol

Self Cite

112

130

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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-␤) and proinflammatory cytokine production through activation of TANKbinding 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 Japanese encephalitis virus (JEV), a member of the family Flaviviridae that causes Japanese encephalitis (JE), is the most common mosquito-borne encephalitis virus in the Japanese encephalitis virus (JEV), a member of the family Flaviviridae, is a single-stranded, positive-sense RNA virus that causes Japanese encephalitis (JE) (1, 2). JE is endemic in most Southeast Asian countries (3, 4). The availability of an effective vaccine and an active immunization program have resulted in a reduced number of JE cases in a few countries (5). The early clinical features of JE include fever, headache, and vomiting. Two weeks after JEV infection, patients develop neurological symptoms, like seizure, tremor, photophobia, and movement disorder (6). These clinical features are not exclusive to JEV infection, and hence, laboratory diagnosis is needed to differentiate it from other neurological disorders. Detection of anti-JEV IgM antibodies in the cerebrospinal fluid (CSF) and serum is frequently used to diagnose JE (7). The fatality rate of JEV infection is ϳ25%. A majority of survivors (ϳ50%) have neuropsychiatric sequelae; only ϳ25% recover completely (8). Hence, JEV poses major health concerns and economic burdens in the Asia-Pacific region. During the last decade, we and others have made significant progress in the understanding molecular mechanisms involved in JEV infection.MicroRNAs (miRNAs) are small, noncoding RNAs ϳ19 to 22 nucleotides in length that regulate various cellular processes by binding to the 3= untranslated region (UTR) of target proteins, resulting in either degradation of RNA or translational suppression (9, 10). Our knowledge of the role of miRNAs in various diseases is expanding rapidly. Various reports support the role of miRNAs in neuroviral...

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“…Similar establishment of NF-jB dysregulation by miRNAtargeting of A20 was observed during Japanese encephalitis virus infection. This virus induced cellular miR-29b expression, which regulated A20 expression in a microglial cell line, thus enhancing NF-jB activity [61]. In stark contrast, another miRNA from the same miR-29 family, miR-29c, was found to be down-regulated in a Hepatitis B Virus (HBV)-related HCC cell line and patient samples.…”

Section: Regulation Of A20 By Micrornasmentioning

confidence: 86%

MicroRNA: master controllers of intracellular signaling pathways

Lui

Jin

Stevenson

2015

Cell. Mol. Life Sci.

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Signaling pathways are essential intracellular networks that coordinate molecular outcomes to external stimuli. Tight regulation of these pathways is essential to ensure an appropriate response. MicroRNA (miRNA) is a class of small, non-coding RNA that regulates gene expression at a post-transcriptional level by binding to the complementary sequence on target mRNA, thus limiting protein translation. Intracellular pathways are controlled by protein regulators, such as suppressor of cytokine signaling and A20. Until recently, expression of these classical protein regulators was thought to be controlled solely by transcriptional induction and proteasomal degradation; however, there is a growing body of evidence describing their regulation by miRNA. This new information has transformed our understanding of cell signaling by adding a previously unknown layer of regulatory control. This review outlines the miRNA regulation of these classical protein regulators and describes their broad effects at both cellular and disease levels. We review the regulation of three important signaling pathways, including the JAK/STAT, NF-κB, and TGF-β pathways, and summarize an extensive catalog of their regulating miRNAs. This information highlights the importance of the miRNA regulon and reveals a previously unknown regulatory landscape that must be included in the identification and development of novel therapeutic targets for clinical disorders.

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MicroRNA‐29b modulates Japanese encephalitis virus‐induced microglia activation by targeting tumor necrosis factor alpha‐induced protein 3

Cited by 86 publications

References 51 publications

MicroRNA-15b Modulates Japanese Encephalitis Virus–Mediated Inflammation via Targeting RNF125

MicroRNA-15b Modulates Japanese Encephalitis Virus–Mediated Inflammation via Targeting RNF125

MicroRNA 155 Regulates Japanese Encephalitis Virus-Induced Inflammatory Response by Targeting Src Homology 2-Containing Inositol Phosphatase 1

MicroRNA: master controllers of intracellular signaling pathways

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