Bibliographic Details
| Title: |
Chikungunya Virus RNA Secondary Structures Impact Defective Viral Genome Production |
| Authors: |
Laura I. Levi, Emily A. Madden, Jeremy Boussier, Diana Erazo, Wes Sanders, Thomas Vallet, Veronika Bernhauerova, Nathaniel J. Moorman, Mark T. Heise, Marco Vignuzzi |
| Source: |
Microorganisms, Vol 12, Iss 9, p 1794 (2024) |
| Publisher Information: |
MDPI AG, 2024. |
| Publication Year: |
2024 |
| Collection: |
LCC:Biology (General) |
| Subject Terms: |
chikungunya virus, defective viral genome, RNA secondary structure, SHAPE-MaP, Biology (General), QH301-705.5 |
| More Details: |
Chikungunya virus (CHIKV) is a mosquito-borne RNA virus that poses an emerging threat to humans. In a manner similar to other RNA viruses, CHIKV encodes an error-prone RNA polymerase which, in addition to producing full-length genomes, gives rise to truncated, non-functional genomes, which have been 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 the 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 the existing RNA secondary structure (CHIKV-D2S). We show that CHIKV-D2S presents altered DVG generation compared to wild-type virus, correlating with the change in RNA secondary structure obtained by SHAPE-MaP. Our work thus demonstrates that RNA secondary structure impacts CHIKV DVG production during replication. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
2076-2607 |
| Relation: |
https://www.mdpi.com/2076-2607/12/9/1794; https://doaj.org/toc/2076-2607 |
| DOI: |
10.3390/microorganisms12091794 |
| Access URL: |
https://doaj.org/article/00b34d58734a413eb02922eff3e1bfa2 |
| Accession Number: |
edsdoj.00b34d58734a413eb02922eff3e1bfa2 |
| Database: |
Directory of Open Access Journals |
