Extensive and heterogeneous viral circular RNA production during Zika virus infection
- 1Department of Molecular Medicine, University of Padua, via Gabelli 63, 35121, Padova, Italy
Abstract
Circular RNAs (circRNAs) are covalently closed RNA molecules with regulatory functions. Although virus-derived circRNAs (vcircRNAs) are well characterized in DNA viruses, their occurrence in RNA viruses remains poorly understood. Recent reports in coronaviruses and hepatitis C virus suggest that vcircRNA production extends beyond nuclear-replicating viruses. Here, we show that Zika virus (ZIKV), a vector-borne orthoflavivirus, produces vcircRNAs during infection of neural stem cells. Using a custom computational pipeline optimized for viral back-splice junction detection, we identified at 72 hours post infection a core set of 113 putative vcircRNAs shared across three biological replicates and distributed throughout the viral genome. Eight candidates spanning different genomic regions and abundance levels were experimentally validated by rolling-circle reverse transcription and Nanopore sequencing. These findings provide the first evidence of vcircRNA production in an orthoflavivirus, suggesting that circular RNA biogenesis may represent a previously underappreciated feature of RNA virus biology.
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BibTeX
@misc{stradiotto2026extensive,
title = {{Extensive and heterogeneous viral circular RNA production during Zika virus infection}},
author = {M. Stradiotto and A. Vezzi and M. Vardeu and B. Mercorelli and S. Vogiatzis and A. Loregian and L. Barzon and S. Toppo and E. Lavezzo and M. Trevisan},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.28.762464},
url = {https://www.biorxiv.org/content/10.64898/2026.10.28.762464v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Extensive and heterogeneous viral circular RNA production during Zika virus infection
AU - M. Stradiotto
AU - A. Vezzi
AU - M. Vardeu
AU - B. Mercorelli
AU - S. Vogiatzis
AU - A. Loregian
AU - L. Barzon
AU - S. Toppo
AU - E. Lavezzo
AU - M. Trevisan
PY - 2026
DA - 2026/10/28
PB - bioRxiv
DO - 10.64898/2026.10.28.762464
UR - https://www.biorxiv.org/content/10.64898/2026.10.28.762464v1
AB - Circular RNAs (circRNAs) are covalently closed RNA molecules with regulatory functions. Although virus-derived circRNAs (vcircRNAs) are well characterized in DNA viruses, their occurrence in RNA viruses remains poorly understood. Recent reports in coronaviruses and hepatitis C virus suggest that vcircRNA production extends beyond nuclear-replicating viruses. Here, we show that Zika virus (ZIKV), a vector-borne orthoflavivirus, produces vcircRNAs during infection of neural stem cells. Using a custom computational pipeline optimized for viral back-splice junction detection, we identified at 72 hours post infection a core set of 113 putative vcircRNAs shared across three biological replicates and distributed throughout the viral genome. Eight candidates spanning different genomic regions and abundance levels were experimentally validated by rolling-circle reverse transcription and Nanopore sequencing. These findings provide the first evidence of vcircRNA production in an orthoflavivirus, suggesting that circular RNA biogenesis may represent a previously underappreciated feature of RNA virus biology.
ER -