MicroRNA and mRNA Dysregulation in Astrocytes Infected with Zika Virus
Robert A Kozak1, Anna Majer2,3, Mia J Biondi4
1Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada. Rob.kozak@gmail.com.
Abstract:
The Zika virus (ZIKV) epidemic is an ongoing public health concern. ZIKV is a flavivirus reported to be associated with microcephaly, and recent work in animal models demonstrates the ability of the virus to cross the placenta and affect fetal brain development. Recent findings suggest that the virus preferentially infects neural stem cells and thereby deregulates gene expression, cell cycle progression, and increases cell death. However, neuronal stem cells are not the only brain cells that are susceptible to ZIKV and infection of other brain cells may contribute to disease progression. Herein, we characterized ZIKV replication in astrocytes, and profiled temporal changes in host microRNAs (miRNAs) and transcriptomes during infection. We observed the deregulation of numerous processes known to be involved in flavivirus infection, including genes involved in the unfolded protein response pathway. Moreover, a number of miRNAs were upregulated, including miR-30e-3p, miR-30e-5p, and, miR-17-5p, which have been associated with other flavivirus infections. This study highlights potential miRNAs that may be of importance in ZIKV pathogenesis.
Insights
Zika virus (ZIKV) infects astrocytes, altering gene expression and microRNA profiles. This study identifies specific microRNAs potentially involved in ZIKV pathogenesis and disease progression.
Area of Science:
- Neuroscience
- Virology
- Genetics
Background:
- Zika virus (ZIKV) poses a significant public health threat, linked to microcephaly and fetal brain development issues.
- ZIKV preferentially infects neural stem cells, disrupting gene expression, cell cycle, and promoting cell death.
- Other brain cells, such as astrocytes, may also be susceptible to ZIKV infection, contributing to disease progression.
Purpose of the Study:
- To characterize ZIKV replication in astrocytes.
- To profile temporal changes in host microRNAs (miRNAs) and transcriptomes during ZIKV infection of astrocytes.
Main Methods:
- Infection of primary astrocyte cultures with ZIKV.
- Analysis of host miRNA and transcriptome changes over time post-infection using sequencing technologies.
Main Results:
- ZIKV replicates in astrocytes, leading to deregulation of numerous cellular processes, including the unfolded protein response pathway.
- Specific miRNAs, including miR-30e-3p, miR-30e-5p, and miR-17-5p, were found to be upregulated during ZIKV infection.
- These upregulated miRNAs have previously been associated with other flavivirus infections.
Conclusions:
- Astrocytes are a target for ZIKV, and their infection impacts host gene and miRNA expression.
- The identified miRNAs (miR-30e-3p, miR-30e-5p, miR-17-5p) may play a crucial role in ZIKV pathogenesis.
- Further investigation into these miRNAs could reveal therapeutic targets for ZIKV infection.
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