Alterations in microRNA expression profile in rabies virus-infected mouse neurons

Shi, Ning; Xy, Zhang; Cy, Dong; Jl, Hou; Ml, Zhang; Zh, Guan; Zy, Li; Duan, Minghui

doi:10.4149/av_2014_02_120

Cited by 7 publications

(9 citation statements)

References 31 publications

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“…Of the miRNAs with fold change ≥3.0, 5 (miR-155-5p, miR-21-3p, miR-21-5p, miR-223-3p and miR-223-5p) were induced in the brain by both Flury and GX01; 3 (miR-155-5p, miR-223-3p and miR-223-5p) were simultaneously induced in brain and spinal cord by GX01 (Table 2). Our findings on miRNAs differed completely from Zhao and Shi's reports (Zhao et al, 2012a;2012b;Shi et al, 2014), these miRNAs no one the same with Zhao and Shi's findings, suggesting that cause by different virus strain. The data obtained would be very helpful to further explore the relationship between the miRNAs and viral virulence.…”

Section: Discussioncontrasting

confidence: 97%

“…Functional analysis showed that these differentially expressed miRNAs could be involved in many immune-related signaling pathways, such as Jak-STAT, MAPK, cytokine-cytokine receptor interactions and Fc gamma R-mediated phagocytosis (Zhao et al, 2012a;2012b). In addition, a total of 53 miRNAs were found to be differentially expressed in RABV-infected samples compared with mock samples ( Ghosh et al, 2009;Shi et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

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Differential Expression Analysis of microRNA in the Central Nervous System of Mouse Infected with Rabies Virus

Pan¹

2019

PVJ

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Cellular microRNAs (miRNAs) play a key role in regulating the replication of rabies virus (RABV). To better understand the pathogenesis of RABV, we investigated the miRNAs expression in mice brain and spinal cord during RABV infection in the present study. The results showed the differential expression of 18 (12 up-and 6 down-regulation) and 5 (4 up-and 1 down-regulation) miRNAs with at least 3-fold change in the brain and spinal cord of GX01-infected mice, respectively. Eight miRNAs (7 up and 1 down-regulation) changed at least 3-fold in the brain of Flury-infected mice. Functional annotation of the differentially expressed miRNAs revealed that they are involved in immune response, biological process, apoptosis, and diseases (including cancer, long-term depression, vascular smooth muscle contraction, etc.). Three primary transcripts, miR-101c, miR-155-5p and miR-223-3p were selected for heterologous expression in BHK-21 cells after cloning into eukaryotic expression vector, pEGFP-C1, containing an eGFP marker. Our assays demonstrated that an increase in the N mRNA of RABV occurs in consistent with the up-regulated expression of the miRNAs, suggesting that these miRNAs are likely to be involved in promoting RABV transcription. ©2018 PVJ. All rights reserved Key words: KEGG pathway analysis microRNA (miRNA) RABV To Cite This Article: Pan Y, Xie LJ, Wei XK, Li XN, Liang JJ and Luo TR, 2019. Differential expression analysis of microRNA in the central nervous system of mouse infected with rabies virus. Pak Vet J, 39(1): 49-55. http://dx.

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Section: Discussioncontrasting

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Differential Expression Analysis of microRNA in the Central Nervous System of Mouse Infected with Rabies Virus

Pan¹

2019

PVJ

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“…Recently, transcriptome profiling revealed the differential expression pattern of long noncoding RNAs (lncRNAs) and miRNAs in RABV infection, and their involvement in multiple immunity-related signal pathways [ 53 , 54 , 55 , 56 , 57 ]. Tu et al reported that miR-455-5p promotes viral replication via the SOCS3/STAT3/IL-6 pathway [ 58 ].…”

Section: Discussionmentioning

confidence: 99%

Expression Profiling and Bioinformatics Analysis of CircRNA in Mice Brain Infected with Rabies Virus

Zhao

Wang

et al. 2021

IJMS

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Rabies virus (RABV) induces acute, fatal encephalitis in mammals including humans. The circRNAs are important in virus infection process, but whether circRNAs regulated RABV infection remains largely unknown. Here, mice brain with or without the RABV CVS-11 strain were subjected to RNA sequencing and a total of 30,985 circRNAs were obtained. Among these, 9021 candidates were shared in both groups, and 14,610 and 7354 circRNAs were expressed specifically to the control and experimental groups, indicating that certain circRNAs were specifically inhibited or induced on RABV infection. The circRNAs mainly derived from coding exons. In total, 636 circRNAs were differentially expressed in RABV infection, of which 426 significantly upregulated and 210 significantly downregulated (p < 0.05 and fold change ≥2). The expression of randomly selected 6 upregulated and 6 downregulated circRNAs was tested by RT-qPCR, and the expression trend of the 11 out of 12 circRNAs was consistent in RT- qPCR and RNA-seq analysis. Rnase R-resistant assay and Sanger sequencing were conducted to verify the circularity of circRNAs. GO analysis demonstrated that source genes of all differentially regulated circRNAs were mainly related to cell plasticity and synapse function. Both KEGG and GSEA analysis revealed that these source genes were engaged in the cGMP–PKG and MAPK signaling pathway, and HTLV-I infection. Also, pathways related to glucose metabolism and synaptic functions were enriched in KEGG analysis. The circRNA–miRNA–mRNA network was built with 25 of 636 differentially expressed circRNAs, 264 mRNAs involved in RABV infection, and 29 miRNAs. Several miRNAs and many mRNAs in the network were reported to be related to viral infection and the immune response, suggesting that circRNAs could regulate RABV infection via interacting with miRNAs and mRNAs. Taken together, this study first characterized the transcriptomic pattern of circRNAs, and signaling pathways and function that circRNAs are involved in, which may indicate directions for further research to understand mechanisms of RABV pathogenesis.

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“…miR-135a-5p is a negative regulator of STAT3 phosphatase PTPRD and is upregulated in HCV-infected hepatocytes, leading to enhanced STAT3 transcription (49). Some miRNAs, including miR-124, miR-20, and miR-29a, have been reported to be altered in RABV-infected mouse brain and neurons and have been predicted to contribute to immune modulation (34,35,50). These observations led to our hypothesis that the RABV-induced dysregulation of SOCS3/STAT3 was mediated by miRNAs.…”

Section: Discussionmentioning

confidence: 99%

“…Two EBV-encoded genes (LMP1 and EBNA2) are known to promote the expression of miR-155, which is required for the growth of EBV-infected B cells and lymphoma development (33). Several miRNAs, such as miR-124, miR-20, and miR-29a, have been implicated in the RABV infection process by contributing to neuronal dysfunction, while miR-190, miR-203, and miR-145 regulate viral infection-associated JAK-STAT, the T-cell receptor signaling pathway, and natural killer cell-mediated cytotoxicity (34,35). Recent evidence that miR-20a and miR-124 are responsible for neuroremodeling has been obtained (36,37); however, whether the RABV-induced dysregulation of the SOCS3/STAT3 pathway is mediated by miRNAs remains unclear.…”

mentioning

confidence: 99%

Pentagalloylglucose Inhibits the Replication of Rabies Virus via Mediation of the miR-455/SOCS3/STAT3/IL-6 Pathway

Zhang

et al. 2019

J Virol

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Our previous study showed that pentagalloylglucose (PGG), a naturally occurring hydrolyzable phenolic tannin, possesses significant anti-rabies virus (RABV) activity. In BHK-21 cells, RABV induced the overactivation of signal transducer and activator of transcription 3 (STAT3) by suppressing the expression of suppressor of cytokine signaling 3 (SOCS3). Inhibition of STAT3 by niclosamide, small interfering RNA, or exogenous expression of SOCS3 all significantly suppressed the replication of RABV. Additionally, RABV-induced upregulation of microRNA 455-5p (miR-455-5p) downregulated SOCS3 by directly binding to the 3′ untranslated region (UTR) of SOCS3. Importantly, PGG effectively reversed the expression of miR-455-5p and its following SOCS3/STAT3 signaling pathway. Finally, activated STAT3 elicited the expression of interleukin-6 (IL-6), thereby contributing to RABV-associated encephalomyelitis; however, PGG restored the level of IL-6 in vitro and in vivo in a SOCS3/STAT3-dependent manner. Altogether, these data identify a new miR-455-5p/SOCS3/STAT3 signaling pathway that contributes to viral replication and IL-6 production in RABV-infected cells, with PGG exerting its antiviral effect by inhibiting the production of miR-455-5p and the activation of STAT3. IMPORTANCE Rabies virus causes lethal encephalitis in mammals and poses a serious public health threat in many parts of the world. Numerous strategies have been explored to combat rabies; however, their efficacy has always been unsatisfactory. We previously reported a new drug, PGG, which possesses a potent inhibitory activity on RABV replication. Herein, we describe the underlying mechanisms by which PGG exerts its anti-RABV activity. Our results show that RABV induces overactivation of STAT3 in BHK-21 cells, which facilitates viral replication. Importantly, PGG effectively inhibits the activity of STAT3 by disrupting the expression of miR-455-5p and increases the level of SOCS3 by directly targeting the 3′ UTR of SOCS3. Furthermore, the downregulated STAT3 inhibits the production of IL-6, thereby contributing to a reduction in the inflammatory response in vivo. Our study indicates that PGG effectively inhibits the replication of RABV by the miR-455-5p/SOCS3/STAT3/IL-6-dependent pathway.

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Alterations in microRNA expression profile in rabies virus-infected mouse neurons

Cited by 7 publications

References 31 publications

Differential Expression Analysis of microRNA in the Central Nervous System of Mouse Infected with Rabies Virus

Differential Expression Analysis of microRNA in the Central Nervous System of Mouse Infected with Rabies Virus

Expression Profiling and Bioinformatics Analysis of CircRNA in Mice Brain Infected with Rabies Virus

Pentagalloylglucose Inhibits the Replication of Rabies Virus via Mediation of the miR-455/SOCS3/STAT3/IL-6 Pathway

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