ArticlePLoS pathogens2017
Dengue virus genomic variation associated with mosquito adaptation defines the pattern of viral non-coding RNAs and fitness in human cells.
Article in PLoS pathogens, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.
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Who cites it
79 citing papers in PubMed, 121 citations in OpenAlex.
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- XRN1-Resistant Elements Are Located in the 3'-Terminal Regions of Certain Genome Segments of Jingmenviruses.Viruses · 2026Article
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- Duplication of specialized cis-acting elements SLI and SLIII in the viral RNA 3'UTR enables mosquito-borne orthoflavivirus adaptation to avian hosts.Nucleic acids research · 2026Article
- DMS-MaPseq and DREEM Analyses Implicate the Critical Role of RNA Structural Dynamics in Turnip Yellow Mosaic Virus Pathogenicity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Structural and nonstructural protein divergence correlates with strain-specific vector competence for Zika virus.Parasites & vectors · 2026Article
- An A-rich linker between dengue virus tandem xrRNAs facilitates functional coordination.bioRxiv : the preprint server for biology · 2026Article
- Cellular Biology: Virus-Host Interactions and RNA Structure and Function.Current topics in microbiology and immunology · 2026Review
- A conserved RNA structure at the capsid-coding sequence of Zika virus genome is required for viral replication in a host-dependent manner.Journal of virology · 2025Article
- DENV-2 3'UTR dumbbell structure is a critical factor for viral infection and dissemination inJournal of virology · 2025Article
- Functional RNA Elements in Alphavirus Genomes.Current microbiology · 2025Review
- Exploring the genetic diversity of the 3' untranslated region (UTR) of Dengue virus.Virology journal · 2025Article
- Development of New Live-Attenuated Vaccine Candidates Lacking Antibody-Dependent Enhancement (ADE) Against Dengue.Vaccines · 2025Review
- Tick-borne flavivirus exoribonuclease-resistant RNAs contain a double loop structure.Nature communications · 2025Article
- Genomic hotspots in the DENV-2 serotype (E, NS4B, and NS5 genes) are associated with dengue disease severity in the endemic region of India.PLoS neglected tropical diseases · 2025Article
- Pan-flavivirus analysis reveals sfRNA-independent, 3' UTR-biased siRNA production from an insect-specific flavivirus.Journal of virology · 2024Article
- Structure of Essential RNA Regulatory Elements in the West Nile Virus 3'-Terminal Stem Loop.Journal of molecular biology · 2024Article
- Zika virus non-coding RNAs antagonize antiviral responses by PKR-mediated translational arrest.Nucleic acids research · 2024Article
19 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 4 institutions in 3 countries.
Funding
Abstract
The Flavivirus genus includes a large number of medically relevant pathogens that cycle between humans and arthropods. This host alternation imposes a selective pressure on the viral population. Here, we found that dengue virus, the most important viral human pathogen transmitted by insects, evolved a mechanism to differentially regulate the production of viral non-coding RNAs in mosquitos and humans, with a significant impact on viral fitness in each host. Flavivirus infections accumulate non-coding RNAs derived from the viral 3'UTRs (known as sfRNAs), relevant in viral pathogenesis and immune evasion. We found that dengue virus host adaptation leads to the accumulation of different species of sfRNAs in vertebrate and invertebrate cells. This process does not depend on differences in the host machinery; but it was found to be dependent on the selection of specific mutations in the viral 3'UTR. Dissecting the viral population and studying phenotypes of cloned variants, the molecular determinants for the switch in the sfRNA pattern during host change were mapped to a single RNA structure. Point mutations selected in mosquito cells were sufficient to change the pattern of sfRNAs, induce higher type I interferon responses and reduce viral fitness in human cells, explaining the rapid clearance of certain viral variants after host change. In addition, using epidemic and pre-epidemic Zika viruses, similar patterns of sfRNAs were observed in mosquito and human infected cells, but they were different from those observed during dengue virus infections, indicating that distinct selective pressures act on the 3'UTR of these closely related viruses. In summary, we present a novel mechanism by which dengue virus evolved an RNA structure that is under strong selective pressure in the two hosts, as regulator of non-coding RNA accumulation and viral fitness. This work provides new ideas about the impact of host adaptation on the variability and evolution of flavivirus 3'UTRs with possible implications in virulence and viral transmission.
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