Genetic and phenotypic changes to Venezuelan equine encephalitis virus following treatment with β-D-N4-hydroxycytidine, an RNA mutagen.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
25 Oct 2024
25 Oct 2024
Historique:
received:
27
08
2024
accepted:
16
10
2024
medline:
25
10
2024
pubmed:
25
10
2024
entrez:
25
10
2024
Statut:
epublish
Résumé
The high mutation rate of RNA viruses provides viral populations with the ability to adapt to new environments but also makes them vulnerable to extinction due to the deleterious effects of mutations, which is the conceptual basis for the antiviral activity of RNA mutagens. However, there are still gaps in the quantitative understanding of the dynamics between the mutations induced by an RNA mutagen and its effects on viral fitness. To address this, we used Venezuelan Equine Encephalitis Virus (VEEV) and the potent RNA mutagen β-d-N4-hydroxycytidine (NHC) as a model to analyze virus replication competency and mutation frequency following treatment in the total and replication-competent viral populations separately. We found that NHC induced transition mutations in a concentration dependent manner in the total population, while the replication-competent population maintained itself within an increased, yet narrow, mutation spectrum. The incorporation of NHC mainly happened during the positive sense RNA synthesis of VEEV. A growth kinetic analysis of VEEV population treated with NHC pointed to a lower but more diverse distribution in mutational fitness, demonstrating that NHC-induced mutations negatively and broadly affect the fitness of the virus. Together, our study provides mechanistic insight into how RNA mutagens affect viral population landscape and the potential of RNA mutagens as an antiviral strategy for alphaviruses.
Identifiants
pubmed: 39448734
doi: 10.1038/s41598-024-76788-x
pii: 10.1038/s41598-024-76788-x
doi:
Substances chimiques
Cytidine
5CSZ8459RP
Mutagens
0
N(4)-hydroxycytidine
C3D11PV2O4
RNA, Viral
0
Antiviral Agents
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
25265Subventions
Organisme : NIH HHS
ID : 1U19AI142762
Pays : United States
Organisme : NIH HHS
ID : 1U19AI142762
Pays : United States
Organisme : NIH HHS
ID : 1U19AI142762
Pays : United States
Organisme : NIH HHS
ID : P20GM103436
Pays : United States
Organisme : NIH HHS
ID : P20GM103436
Pays : United States
Organisme : NIH HHS
ID : P30ES030283
Pays : United States
Informations de copyright
© 2024. The Author(s).
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