Version 1
: Received: 15 July 2024 / Approved: 15 July 2024 / Online: 15 July 2024 (17:16:20 CEST)
How to cite:
LEVI, L. I.; Madden, E. A.; Boussier, J.; Erazo, D.; Sanders, W.; Valley, T.; Bernhauerová, V.; Moorman, N. J. J.; Heise, M. T.; Vignuzzi, M. Chikungunya Virus RNA Secondary Structures Impact Defective Viral Genomes Production. Preprints2024, 2024071212. https://doi.org/10.20944/preprints202407.1212.v1
LEVI, L. I.; Madden, E. A.; Boussier, J.; Erazo, D.; Sanders, W.; Valley, T.; Bernhauerová, V.; Moorman, N. J. J.; Heise, M. T.; Vignuzzi, M. Chikungunya Virus RNA Secondary Structures Impact Defective Viral Genomes Production. Preprints 2024, 2024071212. https://doi.org/10.20944/preprints202407.1212.v1
LEVI, L. I.; Madden, E. A.; Boussier, J.; Erazo, D.; Sanders, W.; Valley, T.; Bernhauerová, V.; Moorman, N. J. J.; Heise, M. T.; Vignuzzi, M. Chikungunya Virus RNA Secondary Structures Impact Defective Viral Genomes Production. Preprints2024, 2024071212. https://doi.org/10.20944/preprints202407.1212.v1
APA Style
LEVI, L. I., Madden, E. A., Boussier, J., Erazo, D., Sanders, W., Valley, T., Bernhauerová, V., Moorman, N. J. J., Heise, M. T., & Vignuzzi, M. (2024). Chikungunya Virus RNA Secondary Structures Impact Defective Viral Genomes Production. Preprints. https://doi.org/10.20944/preprints202407.1212.v1
Chicago/Turabian Style
LEVI, L. I., Mark T Heise and Marco Vignuzzi. 2024 "Chikungunya Virus RNA Secondary Structures Impact Defective Viral Genomes Production" Preprints. https://doi.org/10.20944/preprints202407.1212.v1
Abstract
Chikungunya virus (CHIKV) is a mosquito borne RNA virus that poses an emerging threat to humans. As other RNA viruses, CHIKV encodes an error-prone RNA polymerase which, in addition to full-length genomes, gives rise to truncated, non-functional genomes coined defective viral genomes (DVGs). DVGs have been intensively studied in the context of therapy, as they can inhibit viral replication and dissemination in their hosts. In this work, we interrogate the influence of viral RNA secondary structures on the production of CHIKV DVGs. We experimentally map RNA secondary structures of CHIKV genome using selective 2′-hydroxyl acylation analyzed by primer extension and mutational profiling (SHAPE-MaP), which couples chemical labelling with next-generation sequencing. We correlate the inferred secondary structure with preferred deletion sites of CHIKV DVGs. We document an increased probability of DVG generation with truncations at unpaired nucleotides within the secondary structure. We then generated a CHIKV mutant bearing synonymous changes at the nucleotide level to disrupt existing RNA secondary structure (CHIKV-D2S). We show that CHIKV-D2S presents altered DVG generation compared to wild-type virus, correlating with its change in RNA secondary structure obtained by SHAPE-MaP. Our work thus demonstrates that RNA secondary structure impacts CHIKV DVG production during replication.
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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