ArticleProceedings of the National Academy of Sciences of the United States of America2020
Positive epistasis between viral polymerase and the 3' untranslated region of its genome reveals the epidemiologic fitness of dengue virus.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
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Who cites it
20 citing papers in PubMed, 27 citations in OpenAlex.
- Dengue virus infection.Nature reviews. Disease primers · 2026Review
- Comparative analysis of flavivirus sfRNA dynamics and secondary structure.Journal of virology · 2026Article
- Comparative analysis of flavivirus sfRNA dynamics and secondary structure.bioRxiv : the preprint server for biology · 2026Article
- The role of mitotype variation and positive epistasis in trait differences between Saccharomyces species.Genetics · 2026Article
- Dengue and severe dengue.Clinical microbiology reviews · 2025Review
- Article
- Toward a Categorization of Virus-ncRNA Interactions in the World of RNA to Disentangle the Tiny Secrets of Dengue Virus.Viruses · 2024Review
- The Dynamic Landscape of Capsid Proteins and Viral RNA Interactions in Flavivirus Genome Packaging and Virus Assembly.Pathogens (Basel, Switzerland) · 2024Review
- Global and cell type-specific immunological hallmarks of severe dengue progression identified via a systems immunology approach.Nature immunology · 2023Article
- Subgenomic Flaviviral RNAs of Dengue Viruses.Viruses · 2023Review
- The anti-immune dengue subgenomic flaviviral RNA is present in vesicles in mosquito saliva and is associated with increased infectivity.PLoS pathogens · 2023Article
- A fast-growing dengue virus mutant reveals a dual role of STING in response to infection.Open biology · 2022Article
- Variability in Susceptibility to Type I Interferon Response and Subgenomic RNA Accumulation Between Clinical Isolates of Dengue and Zika Virus From Oaxaca Mexico Correlate With Replication Efficiency in Human Cells and Disease Severity.Frontiers in cellular and infection microbiology · 2022Article
- Potential role of vector-mediated natural selection in dengue virus genotype/lineage replacements in two epidemiologically contrasted settings.Emerging microbes & infections · 2021Article
- Revisiting dengue virus-mosquito interactions: molecular insights into viral fitness.The Journal of general virology · 2021Article
- Dengue Virus Serotype 2 Intrahost Diversity in Patients with Different Clinical Outcomes.Viruses · 2021Article
- Recent African strains of Zika virus display higher transmissibility and fetal pathogenicity than Asian strains.Nature communications · 2021Article
- Tetraspanins as Potential Therapeutic Candidates for Targeting Flaviviruses.Frontiers in immunology · 2021Review
- Epistatic evidence for gender-dependant slow neurotransmission signalling in substance use disorders: PPP1R12B versus PPP1R1B.EBioMedicine · 2020Article
- Experimental adaptation of dengue virus 1 to Aedes albopictus mosquitoes by in vivo selection.Scientific reports · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Dengue virus (DENV) is a global health threat, causing repeated epidemics throughout the tropical world. While low herd immunity levels to any one of the four antigenic types of DENV predispose populations to outbreaks, viral genetic determinants that confer greater fitness for epidemic spread is an important but poorly understood contributor of dengue outbreaks. Here we report that positive epistasis between the coding and noncoding regions of the viral genome combined to elicit an epidemiologic fitness phenotype associated with the 1994 DENV2 outbreak in Puerto Rico. We found that five amino acid substitutions in the NS5 protein reduced viral genomic RNA (gRNA) replication rate to achieve a more favorable and relatively more abundant subgenomic flavivirus RNA (sfRNA), a byproduct of host 5'-3' exoribonuclease activity. The resulting increase in sfRNA relative to gRNA levels not only inhibited type I interferon (IFN) expression in infected cells through a previously described mechanism, but also enabled sfRNA to compete with gRNA for packaging into infectious particles. We suggest that delivery of sfRNA to new susceptible cells to inhibit type I IFN induction before gRNA replication and without the need for further de novo sfRNA synthesis could form a "preemptive strike" strategy against DENV.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.