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  • In silico analysis revealed Zika virus miRNAs associated with viral pathogenesis through alteration of host genes involved in immune response and neurological functions

    Author(s)
    Islam, MS
    Khan, MAAK
    Murad, MW
    Karim, M
    Islam, ABMMK
    Griffith University Author(s)
    Islam, Md Sajedul
    Year published
    2019
    Metadata
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    Abstract
    Background: The concurrent Zika Virus (ZIKV) outbreaks in the United States and Northeast Brazil have evoked global surveillance. Zika infection has been correlated with severe clinical symptoms, such as microcephaly, Guillain-Barré syndrome, and other congenital brain abnormalities. Recent data suggest that ZIKV predominantly targets neural progenitor cells leading to neurological impairment. Despite the clinical evidence, detailed experimental mechanism of ZIKV neurotropic pathogenesis has not been fully understood yet. Here we hypothesized that ZIKV produces miRNAs, which target essential host genes involved in various ...
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    Background: The concurrent Zika Virus (ZIKV) outbreaks in the United States and Northeast Brazil have evoked global surveillance. Zika infection has been correlated with severe clinical symptoms, such as microcephaly, Guillain-Barré syndrome, and other congenital brain abnormalities. Recent data suggest that ZIKV predominantly targets neural progenitor cells leading to neurological impairment. Despite the clinical evidence, detailed experimental mechanism of ZIKV neurotropic pathogenesis has not been fully understood yet. Here we hypothesized that ZIKV produces miRNAs, which target essential host genes involved in various cellular pathways facilitating their survival through immune evasion and progression of disease during brain development. Methods: From genome sequence information using several bioinformatic tools, we predicted pri-miRNAs, pre-miRNAs, and finally the mature miRNAs produced by ZIKV. We also identified their target genes and performed functional enrichment analysis to identify the biological processes associated with these genes. Finally, we analyzed a publicly available RNA-seq data set to determine the altered expression level of the targeted genes. Results: From ZIKV genome sequence, we identified and validated 47 putative novel miRNAs. Functional enrichment of the targeted genes demonstrates the involvement of various biological pathways regulating cellular signaling, neurological functions, cancer, and fetal development. The expression analysis of these genes showed that ZIKV-produced miRNAs downregulate the key genes involved in these pathways, which in turn may lead to impaired brain development. Conclusions: Our finding proposes novel ZIKV miRNAs and their targets, which upon experimental validation could help developing new therapeutics to combat ZIKV infection and minimize ZIKV-mediated pathologies.
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    Journal Title
    Journal of Medical Virology
    Volume
    91
    Issue
    9
    DOI
    https://doi.org/10.1002/jmv.25505
    Subject
    Zika virus
    functional annotation
    immune response
    miRNA
    neurological functions
    Publication URI
    http://hdl.handle.net/10072/414182
    Collection
    • Journal articles

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