Dengue virus causes changes of MicroRNA-genes regulatory network revealing potential targets for antiviral drugs

Shahen, Mohamed; Guo, Zihu; Shar, Akhtar Hussain; Ebaid, Reham; Qin, Tao; Zhang, Wenjuan; Wu, Ziyin; Bai, Yaofei; Fu, Yingxue; Zheng, Chunli; Wang, He; Shar, Piar Ali; Liu, Jianling; Wang, Zhenzhong; Xiao, Wei; Wang, Yonghua

doi:10.1186/s12918-017-0518-x

Cited by 17 publications

(12 citation statements)

References 64 publications

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“…Having these five drugs independently identified as hits in our screening further confirmed the reliability of the eGFP-JEV based HTS system in identifying potential anti-JEV inhibitors. In addition, it was found that some drugs that had been reported to inhibit other flaviviruses ( Balasubramanian et al, 2017 ; Bullard-Feibelman et al, 2017 ; de Freitas et al, 2019 ; Dong et al, 2019 ; Fryk et al, 2016 , 2017 bib_Fryk_et_al_2016 bib_Fryk_et_al_2017 ; Gan et al, 2018 ; Kuivanen et al, 2017 ; Papin et al, 2005 ; Shahen et al, 2018 ; Simanjuntak et al, 2015 ) could also inhibit JEV. For instance, sofosbuvir, an initially approved nucleotide polymerase inhibitor for the distantly related hepatitis C virus (HCV), were active against a variety of flaviviruses including ZIKV ( Bullard-Feibelman et al, 2017 ), DENV ( Gan et al, 2018 ), YFV ( de Freitas et al, 2019 ) as well as JEV determined here.…”

Section: Discussionmentioning

confidence: 99%

Generation and characterization of Japanese encephalitis virus expressing GFP reporter gene for high throughput drug screening

Zhang

et al. 2020

Antiviral Research

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Japanese encephalitis virus (JEV), a major cause of Japanese encephalitisis, is an arbovirus that belongs to the genus Flavivirus of the family Flaviviridae . Currently, there is no effective drugs available for the treatment of JEV infection. Therefore, it is important to establish efficient antiviral screening system for the development of antiviral drugs. In this study, we constructed a full-length infectious clone of eGFP-JEV reporter virus by inserting the eGFP gene into the capsid-coding region of the viral genome. The reporter virus RNA transfected-BHK-21 cells generated robust eGFP fluorescence signals that were correlated well with viral replication. The reporter virus displayed growth kinetics similar to wild type (WT) virus although replicated a little slower. Using a known JEV inhibitor, NITD008, we demonstrated that the reporter virus could be used to identify inhibitors against JEV. Furthermore, an eGFP-JEV-based high throughput screening (HTS) assay was established in a 96-well format and used for screening of 1443 FDA-approved drugs. Sixteen hit drugs were identified to be active against JEV. Among them, five compounds which are lonafarnib, cetylpyridinium chlorid, cetrimonium bromide, nitroxoline and hexachlorophene, are newly discovered inhibitors of JEV, providing potential new therapies for treatment of JEV infection.

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Section: Discussionmentioning

confidence: 99%

Generation and characterization of Japanese encephalitis virus expressing GFP reporter gene for high throughput drug screening

Zhang

et al. 2020

Antiviral Research

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“…Various microarray analyses demonstrated aberrant miRNA expression in patient’s plasma as a hallmark of DENV infection. Total plasma samples, endothelial cells, macrophages and dendritic cells, all of them have been reported to display altered microRNA profiling upon DENV infection [65–69]. Endothelial migration response, various inflammatory response and viral replication itself was shown to be regulated via different sets of microRNAs [68, 69].…”

Section: Role Of Micrornas In Denv Severitymentioning

confidence: 99%

“…Endothelial migration response, various inflammatory response and viral replication itself was shown to be regulated via different sets of microRNAs [68, 69]. miR-590-3p, miR-146a, miRNA-3614-5p, miR-24-1-5p, miR-512-5p and miR-4640-3p, miR-125, miR34 and many more have been reported to play a critical role at various stages of DENV pathogenesis [65, 68, 70]. Our previous work has also reported the regulation of VE-cadherin, an adherens junction protein to be regulated by miR-101 upon the exposure of HIV-1 Tat protein [71].…”

Section: Role Of Micrornas In Denv Severitymentioning

confidence: 99%

Dengue haemorrhagic fever: a job done via exosomes?

Mishra

Lata

Ali

et al. 2019

Emerging Microbes & Infections

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Dengue fever is one of those unique diseases where host immune responses largely determine the pathogenesis and its severity. Earlier studies have established the fact that dengue virus (DENV) infection causes haemorrhagic fever and shock syndrome, but it is not directly responsible for exhibiting these clinical symptoms. It is noteworthy that clinically, vascular leakage syndrome does not develop for several days after infection despite a robust innate immune response that elicits the production of proinflammatory and proangiogenic cytokines. The onset of hyperpermeability in severe cases of dengue disease takes place around the time of defervescence and after clearance of viraemia. Extracellular vesicles are known to carry biological information (mRNA, miRNA, transcription factors) from their cells of origin and have emerged as a significant vehicle for horizontal transfer of stress signals. In dengue virus infection, the relevance of exosomes can be instrumental since the majority of the immune responses in severe dengue involve heavy secretion and circulation of pro-inflammatory cytokines and chemokines. Here, we present an updated review which will address the unique and puzzling features of hyperpermeability associated with DENV infection with a special focus on the role of secreted extracellular vesicles.

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“…So far, there have been reported several cellular miRNAs (miRNAome) that are modulated during DENV infection of mammalian cells, mainly related to the regulation of IFN-β signaling pathways [185][186][187][188]. Some of these miRNAs have been proposed to be used as biomarkers in dengue-infected patients [189,190]. Interestingly, modulation of microRNA expressions have been also described upon DENV infection of insect cells (e.g., C6/36 cells) as well as adult vector mosquitoes such as Aedes albopictus [191][192][193], suggesting that DENV might also regulate the activation of these antiviral RNAi pathways in vector mosquitoes, potentially avoiding viral clearance that promotes viral replication and transmission [194].…”

Section: Denv Infection and The Host Innate Immune Responsesmentioning

confidence: 99%

Dengue Immunopathogenesis: A Crosstalk between Host and Viral Factors Leading to Disease: Part I - Dengue Virus Tropism, Host Innate Immune Responses, and Subversion of Antiviral Responses

Puerta-Guardo¹,

Biering²,

Harris³

et al. 2020

Dengue Fever in a One Health Perspective

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Dengue is the most prevalent emerging mosquito-borne viral disease, affecting more than 40% of the human population worldwide. Many symptomatic dengue virus (DENV) infections result in a relatively benign disease course known as dengue fever (DF). However, a small proportion of patients develop severe clinical manifestations, englobed in two main categories known as dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Secondary infection with any of the four dengue virus serotypes (DENV1, -2, -3, and -4) is a risk factor to develop severe forms of dengue disease. DSS is primarily characterized by sudden and abrupt endothelial dysfunction, resulting in vascular leak and organ impairment, which may progress to hypovolemic shock and death. Severe DENV disease (DHF/DSS) is thought to follow a complex relationship between distinct immunopathogenic processes involving host and viral factors, such as the serotype cross-reactive antibody-dependent enhancement (ADE), the activation of T cells and complement pathways, the phenomenon of the cytokine storm, and the newly described viral toxin activity of the nonstructural protein 1 (NS1), which together play critical roles in inducing vascular leak and virus pathogenesis. In this chapter that is divided in two parts, we will outline the recent advances in our understanding of DENV pathogenesis, highlighting key viral-host interactions and discussing how these interactions may contribute to DENV immunopathology and the development of vascular leak, a hallmark of severe dengue. Part I will address the general features of the DENV complex, including the virus structure and genome, epidemiology, and clinical outcomes, followed by an updated review of the literature describing the host innate immune strategies as well as the viral mechanisms acting against and in favor of the DENV replication cycle and infection.

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Dengue virus causes changes of MicroRNA-genes regulatory network revealing potential targets for antiviral drugs

Cited by 17 publications

References 64 publications

Generation and characterization of Japanese encephalitis virus expressing GFP reporter gene for high throughput drug screening

Generation and characterization of Japanese encephalitis virus expressing GFP reporter gene for high throughput drug screening

Dengue haemorrhagic fever: a job done via exosomes?

Dengue Immunopathogenesis: A Crosstalk between Host and Viral Factors Leading to Disease: Part I - Dengue Virus Tropism, Host Innate Immune Responses, and Subversion of Antiviral Responses

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