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Open AccessArticle

Asian Zika Virus Isolate Significantly Changes the Transcriptional Profile and Alternative RNA Splicing Events in a Neuroblastoma Cell Line

1
Department of Biological Sciences, University at Albany-SUNY, Albany, NY 12222, USA
2
The RNA Institute, University at Albany-SUNY, Albany, NY 12222, USA
3
Department of Biochemistry and Molecular Biology, College of Medicine, University of Florida, Gainesville, FL 32610, USA
4
Wadsworth Center, New York State Department of Health (NYSDOH), Slingerlands, NY 12159, USA
5
Department of Biomedical Sciences, University at Albany-SUNY, School of Public Health, Rensselaer, NY 12144, USA
*
Author to whom correspondence should be addressed.
Viruses 2020, 12(5), 510; https://doi.org/10.3390/v12050510
Received: 9 April 2020 / Accepted: 27 April 2020 / Published: 5 May 2020
(This article belongs to the Special Issue Emerging Arboviruses)
The alternative splicing of pre-mRNAs expands a single genetic blueprint to encode multiple, functionally diverse protein isoforms. Viruses have previously been shown to interact with, depend on, and alter host splicing machinery. The consequences, however, incited by viral infection on the global alternative slicing (AS) landscape are under-appreciated. Here, we investigated the transcriptional and alternative splicing profile of neuronal cells infected with a contemporary Puerto Rican Zika virus (ZIKVPR) isolate, an isolate of the prototypical Ugandan ZIKV (ZIKVMR), and dengue virus 2 (DENV2). Our analyses revealed that ZIKVPR induced significantly more differential changes in expressed genes compared to ZIKVMR or DENV2, despite all three viruses showing equivalent infectivity and viral RNA levels. Consistent with the transcriptional profile, ZIKVPR induced a higher number of alternative splicing events compared to ZIKVMR or DENV2, and gene ontology analyses highlighted alternative splicing changes in genes associated with mRNA splicing. In summary, we show that ZIKV affects cellular RNA homeostasis not only at the transcriptional levels but also through the alternative splicing of cellular transcripts. These findings could provide new molecular insights into the neuropathologies associated with this virus. View Full-Text
Keywords: Zika virus; Flavivirus; SH-SY5Y; transcriptome; alternative splicing Zika virus; Flavivirus; SH-SY5Y; transcriptome; alternative splicing
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Bonenfant, G.; Meng, R.; Shotwell, C.; Badu, P.; Payne, A.F.; Ciota, A.T.; Sammons, M.A.; Berglund, J.A.; Pager, C.T. Asian Zika Virus Isolate Significantly Changes the Transcriptional Profile and Alternative RNA Splicing Events in a Neuroblastoma Cell Line. Viruses 2020, 12, 510.

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