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Integrated MicroRNA and mRNA Profiling in Zika Virus-Infected Neurons

Francine Azouz1, Komal Arora2, Keeton Krause3

  • 1Department of Tropical Medicine, Medical Microbiology and Pharmacology, Pacific Center for Emerging Infectious Diseases Research, John A. Burns School of Medicine, University of Hawai'i at Mānoa, Honolulu, HI 96813, USA. azouzf@hawaii.edu.

Viruses
|February 21, 2019
PubMed

Insights

Zika virus (ZIKV) infection disrupts microRNA (miRNA) regulation in neurons, leading to neurological damage. Understanding these ZIKV-modulated miRNAs and their targets is key for developing new therapies against ZIKV neurological diseases.

Area of Science:

  • Neuroscience
  • Virology
  • Molecular Biology

Background:

  • Zika virus (ZIKV) causes severe neurological diseases, including microcephaly and Guillain-Barré syndrome.
  • Current treatments for ZIKV infections are limited, highlighting the need for novel therapeutic strategies.
  • MicroRNAs (miRNAs) are crucial regulators of cellular processes and have been implicated in viral infections and neurological disorders.

Purpose of the Study:

  • To investigate the impact of ZIKV infection on miRNA and mRNA expression profiles in primary mouse neurons.
  • To identify specific ZIKV-modulated miRNAs and their potential roles in ZIKV-induced neuropathogenesis.
  • To explore the correlation between miRNA dysregulation and host gene expression changes during ZIKV infection.

Main Methods:

  • Digital miRNA and mRNA profiling of ZIKV-infected primary mouse neurons using nCounter technology.
  • Analysis of 599 miRNAs and 770 mRNAs to identify differentially expressed molecules.
  • Bioinformatic analysis to determine the functional pathways regulated by ZIKV-modulated miRNAs and mRNAs.

Main Results:

  • ZIKV infection globally downregulates miRNAs, with a few exceptions, and also reduces miRNA processing enzymes.
  • Specific miRNAs, including miR-155, miR-203, miR-29a, and miR-124-3p, were modulated by ZIKV and are known to be involved in antiviral immunity and brain injury.
  • ZIKV infection upregulates antiviral, inflammatory, and apoptotic genes, showing an inverse correlation with the dysregulated miRNAs.
  • Modulated miRNAs and mRNAs are associated with neurological development and neuroinflammatory pathways.

Conclusions:

  • ZIKV infection profoundly alters miRNA expression in neurons, contributing to neuropathogenesis.
  • The identified ZIKV-modulated miRNAs and their target genes offer potential therapeutic targets for ZIKV-related neurological conditions.
  • Further functional studies on specific miRNAs are essential for developing effective treatments for ZIKV-induced neurological diseases.
Keywords:
Zika virusanti-viral immunityflavivirusmicroRNAsneuroinflammationneurons

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