In silico study identifies hub genes and regulatory network associated with the pathogenesis of Japanese encephalitis virus

Abstract Background Japanese encephalitis (JE) is a mosquito-borne viral disease caused by Japanese encephalitis virus (JEV). Approximately 3 billion people from South-East Asia are at risk of this disease; however, no definitive cure for JE has been developed. Therefore, it is important to understa...

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Main Authors: Arvind Kumar, Gyanendra Bahadur Chand, Gajendra Kumar Azad
Format: Article
Language:English
Published: SpringerOpen 2025-06-01
Series:Egyptian Journal of Medical Human Genetics
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Online Access:https://doi.org/10.1186/s43042-025-00729-0
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author Arvind Kumar
Gyanendra Bahadur Chand
Gajendra Kumar Azad
author_facet Arvind Kumar
Gyanendra Bahadur Chand
Gajendra Kumar Azad
author_sort Arvind Kumar
collection DOAJ
description Abstract Background Japanese encephalitis (JE) is a mosquito-borne viral disease caused by Japanese encephalitis virus (JEV). Approximately 3 billion people from South-East Asia are at risk of this disease; however, no definitive cure for JE has been developed. Therefore, it is important to understand the biology of JE by identifying critical genes and miRNAs involved in the pathogenesis. Therefore, this study was undertaken to identify hub genes and regulatory network associated with JE pathogenesis using several computational tools such as GEO2R, GeneMania, Cytohubba, WebGestalt, miRTarBase and mathematical modelling. Results Our data revealed VEGFA and WNT5A genes are major contributing factors for the development of primary stage of invasive JEV. These two genes were found to be regulated by transcription factor and miRNA targets from multiple databases. The analysis revealed that the activation of VEGFA and WNT5A are mediated by several transcription factors (TFs) that include EGR1, EPAS1, ETS1, FOS, HIF1A and GLI3, GLI2, GLI1, respectively. Furthermore, we also identified hsa-miR-205 and hsa-miR-330-5p miRNAs that regulates the repression of VEGFA and WNT5A. The mathematical modelling supports the role of these two miRNAs in the initiation of the regulatory pathogenesis in JEV. Additionally, we have shown that the type 1 and type 2 coherent and incoherent feed forward loops help to determine the VEGFA gene regulation by TFs and miRNAs. Conclusions This study provides potential new insights into the molecular mechanisms connecting JEV with VEGFA/WNT5A via miRNAs. Altogether, studies on JE pathogenesis will help to identify drug targets and also develop new strategies for JE treatment.
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spelling doaj-art-9bce5d5d2e5348b9b489a64c5f2c84dd2025-08-20T03:26:44ZengSpringerOpenEgyptian Journal of Medical Human Genetics2090-24412025-06-0126111410.1186/s43042-025-00729-0In silico study identifies hub genes and regulatory network associated with the pathogenesis of Japanese encephalitis virusArvind Kumar0Gyanendra Bahadur Chand1Gajendra Kumar Azad2Central University of South BiharDepartment of Zoology, Patna UniversityMolecular Biology Laboratory, Department of Zoology, Patna UniversityAbstract Background Japanese encephalitis (JE) is a mosquito-borne viral disease caused by Japanese encephalitis virus (JEV). Approximately 3 billion people from South-East Asia are at risk of this disease; however, no definitive cure for JE has been developed. Therefore, it is important to understand the biology of JE by identifying critical genes and miRNAs involved in the pathogenesis. Therefore, this study was undertaken to identify hub genes and regulatory network associated with JE pathogenesis using several computational tools such as GEO2R, GeneMania, Cytohubba, WebGestalt, miRTarBase and mathematical modelling. Results Our data revealed VEGFA and WNT5A genes are major contributing factors for the development of primary stage of invasive JEV. These two genes were found to be regulated by transcription factor and miRNA targets from multiple databases. The analysis revealed that the activation of VEGFA and WNT5A are mediated by several transcription factors (TFs) that include EGR1, EPAS1, ETS1, FOS, HIF1A and GLI3, GLI2, GLI1, respectively. Furthermore, we also identified hsa-miR-205 and hsa-miR-330-5p miRNAs that regulates the repression of VEGFA and WNT5A. The mathematical modelling supports the role of these two miRNAs in the initiation of the regulatory pathogenesis in JEV. Additionally, we have shown that the type 1 and type 2 coherent and incoherent feed forward loops help to determine the VEGFA gene regulation by TFs and miRNAs. Conclusions This study provides potential new insights into the molecular mechanisms connecting JEV with VEGFA/WNT5A via miRNAs. Altogether, studies on JE pathogenesis will help to identify drug targets and also develop new strategies for JE treatment.https://doi.org/10.1186/s43042-025-00729-0Japanese encephalitis virusHub genesmiRNAsWNT5AVEGFARegulatory networks
spellingShingle Arvind Kumar
Gyanendra Bahadur Chand
Gajendra Kumar Azad
In silico study identifies hub genes and regulatory network associated with the pathogenesis of Japanese encephalitis virus
Egyptian Journal of Medical Human Genetics
Japanese encephalitis virus
Hub genes
miRNAs
WNT5A
VEGFA
Regulatory networks
title In silico study identifies hub genes and regulatory network associated with the pathogenesis of Japanese encephalitis virus
title_full In silico study identifies hub genes and regulatory network associated with the pathogenesis of Japanese encephalitis virus
title_fullStr In silico study identifies hub genes and regulatory network associated with the pathogenesis of Japanese encephalitis virus
title_full_unstemmed In silico study identifies hub genes and regulatory network associated with the pathogenesis of Japanese encephalitis virus
title_short In silico study identifies hub genes and regulatory network associated with the pathogenesis of Japanese encephalitis virus
title_sort in silico study identifies hub genes and regulatory network associated with the pathogenesis of japanese encephalitis virus
topic Japanese encephalitis virus
Hub genes
miRNAs
WNT5A
VEGFA
Regulatory networks
url https://doi.org/10.1186/s43042-025-00729-0
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AT gyanendrabahadurchand insilicostudyidentifieshubgenesandregulatorynetworkassociatedwiththepathogenesisofjapaneseencephalitisvirus
AT gajendrakumarazad insilicostudyidentifieshubgenesandregulatorynetworkassociatedwiththepathogenesisofjapaneseencephalitisvirus