Dengue Virus RNA Structure Specialization Facilitates Host Adaptation

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Important viral pathogens, such as influenza and dengue, jump between species; however, it is still unclear how these viruses evolved for efficient replication in significantly different environments. Using dengue virus as a model, which naturally alternates between humans and mosquitoes, changes in the viral RNA were investigated in each host. Deep sequencing analysis revealed the selection of strikingly different viral populations during host adaptation. Fitness measurements indicated that mutations in a single RNA structure of the viral 3’ untranslated region were responsible for positive and negative selection of specific viral variants in the two hosts. Cycles of disruption and reconstitution of this RNA structure were observed during host switching, identifying a host adaptable RNA element. Importantly, natural duplication of this RNA was found to be required to tolerate mosquito-associated mutations for efficient replication in mammalian cells. Our studies revealed a novel strategy of viral adaptation, where RNA structure specialization and duplication provide a mechanism for maintaining high viral fitness in each host and efficiency during host cycling. Because the identified RNA structure and its duplication are conserved in many mosquito-borne flaviviruses, our findings using dengue virus could help to understand RNA evolution of an extensive group of human pathogens.

Vyšlo v časopise: Dengue Virus RNA Structure Specialization Facilitates Host Adaptation. PLoS Pathog 11(1): e32767. doi:10.1371/journal.ppat.1004604
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004604

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