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Computational identification of mutually homologous Zika virus miRNAs that target microcephaly genes
Ewen McLean1, Roshan Bhattarai1, Brandon W Hughes1
1a Department of Biology, South Carolina Center for Biotechnology , Claflin University , SC , USA.
Abstract:
Background Zika virus (ZIKV) has been associated with a variety of neuropathologies, including microcephaly. We hypothesize that ZIKV genes activate host microRNAs (miRNAs) causing dysfunctional development of human fetal brains. Objectives/methods A bioinformatics search for miRNA genome-wide binding sites in the prototypic ZIKV (strain MR766) was undertaken to hunt for miRNAs with significant similarities with MCPH genetic sequences responsible for inducing MCHP in human fetal brains. Results Six ZIKV miRNAs were found to share mutual homology with 12 MCPH genetic sequences responsible for inducing MCPH. Noteworthy was miR-1304, which expressed 100% identity to six different MCPH genes. Conclusions We suggest that following infection of fetal neurons ZIKV may modulate the action of various miRNAs, and miR-1304 in particular, resulting in microcephaly.
Insights
Zika virus (ZIKV) may cause microcephaly by activating host microRNAs (miRNAs). Specifically, ZIKV genes might interact with miRNAs, disrupting human fetal brain development and leading to microcephaly.
Area of Science:
- Virology
- Neuroscience
- Genetics
Background:
- Zika virus (ZIKV) is linked to severe neuropathologies, notably microcephaly.
- The precise mechanisms by which ZIKV affects fetal brain development remain under investigation.
Purpose of the Study:
- To investigate the hypothesis that ZIKV genes activate host microRNAs (miRNAs).
- To identify specific miRNAs and their interactions with genetic sequences implicated in microcephaly.
Main Methods:
- Bioinformatic analysis of ZIKV (strain MR766) genome-wide miRNA binding sites.
- Comparative analysis of ZIKV-associated miRNAs and microcephaly (MCPH) genetic sequences.
Main Results:
- Six ZIKV-derived miRNAs showed homology with 12 MCPH genetic sequences.
- miR-1304 exhibited 100% sequence identity with six distinct MCPH genes.
Conclusions:
- ZIKV infection in fetal neurons may lead to microcephaly.
- This process likely involves the modulation of host miRNAs, particularly miR-1304, by ZIKV.