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

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 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.

Duck Tembusu Virus Utilizes miR-221-3p Expression to Facilitate Viral Replication via Targeting of Suppressor of Cytokine Signaling 5

“…Viral infection triggers the innate immune response (Satoshi and Shizuo, 2006;Koyama et al, 2008). Moreover, viralinduced immune response is also closely related to miRNAsmediated post-transcriptional gene silencing mechanism (Xiao and Rajewsky, 2009;Chang Zheng et al, 2013;Islam et al, 2019;Rastogi and Singh, 2019). SOCS5, a negative regulator of cytokine and growth factor signaling, belonging to the SOCS family (Yoh Ichi et al, 2002;Edith et al, 2005;Nicholson et al, 2005;Kedzierski et al, 2017).…”

“…miRNAs, a highly conversed non-coding small RNAs of about 22nt in length, play key regulator roles in gene expression through transcription repression or mRNA destabilization via suppression of gene expression by binding to the complementary sequences in 3-untranslated region (UTR) of target mRNAs (Bartel, 2004;Lin and Hannon, 2004;Victor, 2004;Fabbri et al, 2007). It is now well documented that there is a correlation between miRNAs expression and viral infection (Ojha et al, 2016;Trobaugh and Klimstra, 2017;Hussein et al, 2019;Islam et al, 2019;Sartorius et al, 2019). In particular, recent studies further suggested that the expression profiles of host miRNAs were changed or viral miRNAs were generated during viral infection (Skalsky and Cullen, 2006;Kincaid and Sullivan, 2012;Castro et al, 2019).…”

Epigenetic regulator miRNA pattern differences among SARS-CoV, SARS-CoV-2 and SARS-CoV-2 world-wide isolates delineated the mystery behind the epic pathogenicity and distinct clinical characteristics of pandemic COVID-19

“…A summary discussed that number of DNA and RNA viruses produce miRNAs known as viral miRNAs (v-miRNAs) to evade the host immune response (Mishra et al, 2020). Novel viral miRNAs have been predicted to play an important role in neurological disorders as well (Islam et al, 2019). Among RNA viruses, for example, HIV-1 encoded miR-H1 can cause mononuclear cells apoptosis; H5N1 influenza virus-encoded miR-HA-3p targets host PCBP2 and contributes to ‘cytokine storm’ and mortality, and KUN-miR-1 of West Nile virus targets host’s GATA4 which facilitates virus replication (Li and Zou, 2019).…”

“…Novel classes of ncRNAs have been also observed by studies those might play a definitive role in pathogenesis and survival (Liu et al, 2018). Respiratory viral infections caused by influenza, rhinovirus, adenovirus, RSV and coronaviruses can be related to aberrant host miRNA expression and their effect on host can be like - cell apoptosis, inhibition of immunologic pathways, down regulation of host antiviral responses etc (Mallick et al, 2009; Bondanese et al, 2014; Islam et al, 2019; Li and Zou, 2019; Mishra et al, 2020). Transmissible gastroenteritis virus (TGEV) although induce significant IFN-I production after infection by inducing endoplasmic reticulum (ER), it can evade antiviral effect of IFN-I by downregulating miR-30a-5p that normally enhances IFN-I antiviral activity (Ma et al, 2018).…”

“…On the other hand, SARS-CoV-2 has infected many countries, and which resulted a stable mutation rate and resulted some variation (Cullen, 2006; Dykxhoorn, 2007). There are evidence that viral pathogens can have novel immune evasion role by utilizing host miRNA (Islam et al, 2019; Mishra et al, 2020).…”