MicroRNA-23b Inhibits Enterovirus 71 Replication through Downregulation of EV71 VPl Protein

Wen, Bai-Ping; Dai, Hongjian; Yang, Ying; Yu, Zhuang; Sheng, Ru

doi:10.1159/000348504

Cited by 59 publications

(48 citation statements)

References 27 publications

(34 reference statements)

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“…5b). The expression pattern determined by miRNA sequencing was confirmed by taqman RT-qPCR for 2 miRNAs that were described in the literature to be related to enteroviral infection: miR-146a-5p (upregulated) and miR-23b (downregulated) [45][46][47][48] ( Fig. 5c-d).…”

Section: Pattern Of Cellular Mirnas In Ductal-like Cells Persistentlysupporting

confidence: 53%

Persistence of Coxsackievirus B4 in pancreatic ductal-like cells results in cellular and viral changes

et al. 2017

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Introduction: Although known as cytolytic viruses, group B coxackieviruses (CVB) are able to establish a persistent infection in vitro and in vivo. Viral persistence has been reported as a key mechanism in the pathogenesis of CVB-associated chronic diseases such as type 1 diabetes (T1D). The impact of CVB4 persistence on human pancreas ductal-like cells was investigated. Methods: A persistent CVB4 infection was established in ductal-like cells. PDX-1 expression, resistance to CVB4-induced lysis and CAR expression were evaluated. The profile of cellular microRNAs (miRNAs) was investigated through miRNA-sequencing. Viral phenotypic changes were examined, and genomic modifications were assessed by sequencing of the viral genome. Results: The CVB4 persistence in ductal-like cells was productive, with continuous release of infectious particles. Persistently infected cells displayed a resistance to CVB4-induced lysis upon superinfection and expression of PDX-1 and CAR was decreased. These changes were maintained even after virus clearance. The patterns of cellular miRNA expression in mock-infected and in CVB4-persistently infected ductal-like cells were clearly different. The persistent infection-derived virus (PIDV) was still able to induce cytopathic effect but its plaques were smaller than the parental virus. Several mutations appeared in various PIDV genome regions, but amino acid substitutions did not affect the predicted site of interaction with CAR. Conclusion: Cellular and viral changes occur during persistent infection of human pancreas ductal-like cells with CVB4. The persistence of cellular changes even after virus clearance supports the hypothesis of a long-lasting impact of persistent CVB infection on the cells.

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Section: Pattern Of Cellular Mirnas In Ductal-like Cells Persistentlysupporting

confidence: 53%

Persistence of Coxsackievirus B4 in pancreatic ductal-like cells results in cellular and viral changes

et al. 2017

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“…[34][35][36] Whereas to date no data on human CVB3 infections were available, several miRs influenced enterovirus replication in cell and animal models. miR-23b 37 and miR-296-5p (suppressed in CVB3-PERS) inhibit enterovirus 71 replication. 38 miR-23b, and miR-146b, 45 but none of these miRs were differentially expressed in CVB3-ELIM versus CVB3-PERS.…”

Section: Possible Origins Of Differential Mir Expression In Patients mentioning

confidence: 99%

Differential Cardiac MicroRNA Expression Predicts the Clinical Course in Human Enterovirus Cardiomyopathy

Kuehl

Laßner

Gast

et al. 2015

Circ: Heart Failure

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Background— Investigation of disease pathogenesis confined to protein-coding regions of the genome may be incomplete because many noncoding variants are associated with disease. We aimed to identify novel predictive markers for the course of enterovirus (CVB3) cardiomyopathy by screening for noncoding elements influencing the grossly different antiviral capacity of individual patients. Methods and Results— Transcriptome mapping of CVB3 cardiomyopathy patients revealed distinctive cardiac microRNA (miR) patterns associated with spontaneous virus clearance and recovery (CVB3-ELIM) versus virus persistence and progressive clinical deterioration (CVB3-PERS). Profiling of protein-coding genes and 754 miRs in endomyocardial biopsies of test cohorts was performed at their initial presentation, and those spontaneously eliminating the virus were compared with those with virus persistence on follow-up. miR profiling revealed highly significant differences in cardiac levels of 16 miRs, but not of protein-coding genes. Evaluation of this primary distinctive miR pattern in validation cohorts, and multivariate receiver operating characteristic curve analysis, confirmed this pattern as highly predictive for disease course (area under the curve, 0.897±0.071; 95% confidence interval, 0.758–1.000). Eight miRs were strongly induced in CVB3-PERS (miRs 135b, 155, 190, 422a, 489, 590, 601, 1290), but undetectable in CVB3-ELIM or controls. They are predicted to target multiple immune response genes, and 2 of these were confirmed by antisense-mediated ablation of miRs 135b, 190, and 422a in the monocytic THP-1 cell line. Conclusions— An immediate clinical application of the data is cardiac miR profiling to assess the risk of virus persistence and progressive clinical deterioration in CVB3 cardiomyopathy. Patients at risk are eligible for immediate antiviral therapy to minimize irreversible cardiac damage.

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“…On the one hand, host miRNAs may target the viral genome directly to suppress viral replication. Wen et al [35] have reported that miRNA-23b expression is downregulated by EV71 infection and that this miRNA inhibits viral replication via suppression of the structural protein VP1. In addition, Zheng et al [36] have reported that hsa-miR-295-5p expression is upregulated by EV71 infection and that this miRNA suppresses viral replication by targeting the VP1 and VP3 coding regions.…”

Section: Discussionmentioning

confidence: 99%

Hsa-let-7c-5p augments enterovirus 71 replication through viral subversion of cell signaling in rhabdomyosarcoma cells

Zhou

Chu

et al. 2017

Cell Biosci

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BackgroundHuman enterovirus 71 (EV71) causes severe hand, foot and mouse disease, accompanied by neurological complications. During the interaction between EV71 and the host, the virus subverts host cell machinery for its own replication. However, the roles of microRNAs (miRNAs) in this process remain obscure.ResultsIn this study, we found that the miRNA hsa-let-7c-5p was significantly upregulated in EV71-infected rhabdomyosarcoma cells. The overexpression of hsa-let-7c-5p promoted replication of the virus, and the hsa-let-7c-5p inhibitor suppressed viral replication. Furthermore, hsa-let-7c-5p targeted mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) and inhibited its expression. Interestingly, downregulation of MAP4K4 expression led to an increase in EV71 replication. In addition, MAP4K4 knockdown or transfection with the hsa-let-7c-5p mimic led to activation of the c-Jun NH2-terminal kinase (JNK) signaling pathway, whereas the hsa-let-7c-5p inhibitor inhibited activation of this pathway. Moreover, EV71 infection promoted JNK pathway activation to facilitate viral replication.ConclusionsOur data suggested that hsa-let-7c-5p facilitated EV71 replication by inhibiting MAP4K4 expression, which might be related to subversion of the JNK pathway by the virus. These results may shed light on a novel mechanism underlying the defense of EV71 against cellular responses. In addition, these findings may facilitate the development of new antiviral strategies for use in future therapies.Electronic supplementary materialThe online version of this article (doi:10.1186/s13578-017-0135-9) contains supplementary material, which is available to authorized users.

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MicroRNA-23b Inhibits Enterovirus 71 Replication through Downregulation of EV71 VPl Protein

Cited by 59 publications

References 27 publications

Persistence of Coxsackievirus B4 in pancreatic ductal-like cells results in cellular and viral changes

Persistence of Coxsackievirus B4 in pancreatic ductal-like cells results in cellular and viral changes

Differential Cardiac MicroRNA Expression Predicts the Clinical Course in Human Enterovirus Cardiomyopathy

Hsa-let-7c-5p augments enterovirus 71 replication through viral subversion of cell signaling in rhabdomyosarcoma cells

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