In silico analysis revealed Zika virus miRNAs associated with viral pathogenesis through alteration of host genes involved in immune response and neurological functions
| Autor: | Islam Abmmk, Marwah Karim, Muhammad Asif Hossain Khan, Murad Mw, Md. Sajedul Islam |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Microcephaly
In silico Viral pathogenesis Genome Viral Computational biology Disease Biology Zika virus 03 medical and health sciences 0302 clinical medicine Virology microRNA medicine Humans Gene Regulatory Networks 030212 general & internal medicine Gene Zika Virus Infection Mechanism (biology) Gene Expression Profiling Genomics Zika Virus biology.organism_classification medicine.disease MicroRNAs Infectious Diseases Gene Expression Regulation Host-Pathogen Interactions RNA Viral RNA Interference 030211 gastroenterology & hepatology Disease Susceptibility Nervous System Diseases Signal Transduction |
| Zdroj: | Journal of Medical Virology. 91:1584-1594 |
| ISSN: | 1096-9071 0146-6615 |
| Popis: | 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-Barre 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text