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Evolution of subgenomic RNA shapes dengue virus adaptation and epidemiological fitness

Finol, Esteban and Ooi, Eng Eong. (2019) Evolution of subgenomic RNA shapes dengue virus adaptation and epidemiological fitness. iScience, 16. pp. 94-105.

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Abstract

Changes in dengue virus (DENV) genome affect viral fitness both clinically and epidemiologically. Even in the 3' untranslated region (3' UTR), mutations could affect subgenomic flaviviral RNA (sfRNA) production and its affinity for host proteins, which are necessary for successful viral replication. Indeed, we recently showed that mutations in DENV2 3' UTR of epidemic strains increased sfRNA ability to bind host proteins and reduce interferon expression. However, whether 3' UTR differences shape the overall DENV evolution remains incompletely understood. Herein, we combined RNA phylogeny with phylogenetics to gain insights on sfRNA evolution. We found that sfRNA structures are under purifying selection and highly conserved despite sequence divergence. Only the second flaviviral nuclease-resistant RNA (fNR2) structure of DENV2 sfRNA has undergone strong positive selection. Epidemiological reports suggest that substitutions in fNR2 may drive DENV2 epidemiological fitness, possibly through sfRNA-protein interactions. Collectively, our findings indicate that 3' UTRs are important determinants of DENV fitness in human-mosquito cycles.
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH)
UniBasel Contributors:Finol, Esteban
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Elsevier
e-ISSN:2589-0042
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
Identification Number:
Last Modified:02 Jul 2019 07:16
Deposited On:02 Jul 2019 07:16

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