ArticleScientific reports2016
Molecular determinants of plaque size as an indicator of dengue virus attenuation.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed.
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- Domperidone inhibits dengue virus infection by targeting the viral envelope protein and nonstructural protein 1.Scientific reports · 2025Article
- Genetic diversity of dengue virus circulating in the Philippines (2014-2019) and comparison with dengue vaccine strains.PLoS neglected tropical diseases · 2024Article
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- Reemergence of Oropouche virus between 2023 and 2024 in Brazil.medRxiv : the preprint server for health sciences · 2024Article
- Cytokinins Reduce Viral Replication and Alter Plaque Morphology of Frog Virus 3 In Vitro.Viruses · 2024Article
- Attenuation of neurovirulence of chikungunya virus by a single amino acid mutation in viral E2 envelope protein.Journal of biomedical science · 2024Article
- Flavivirus genome recoding by codon optimisation confers genetically stable in vivo attenuation in both mice and mosquitoes.PLoS pathogens · 2023Article
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- 2019-2020 H1N1 clade A5a.1 viruses have better in vitro fitness compared with the co-circulating A5a.2 clade.Scientific reports · 2023Article
- Consensus insertion/deletions and amino acid variations of all coding and noncoding regions of the SARS-CoV-2 Omicron clades, including the XBB and BQ.1 lineages.Archives of virology · 2023Article
- Insights into In Vitro Adaptation of EV71 and Analysis of Reduced Virulence by In Silico Predictions.Vaccines · 2023Article
- 2019-20 H1N1 clade A5a.1 viruses have betterbioRxiv : the preprint server for biology · 2023Article
- A fast-growing dengue virus mutant reveals a dual role of STING in response to infection.Open biology · 2022Article
- Immunological and Pathological Peculiarity of Severe Acute Respiratory Syndrome Coronavirus 2 Beta Variant.Microbiology spectrum · 2022Article
- DNA Origami Disguises Herpes Simplex Virus 1 Particles and Controls Their Virulence.Molecules (Basel, Switzerland) · 2022Article
Corrections and comments
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16 authors.
Funding
Abstract
The development of live viral vaccines relies on empirically derived phenotypic criteria, especially small plaque sizes, to indicate attenuation. However, while some candidate vaccines successfully translated into licensed applications, others have failed safety trials, placing vaccine development on a hit-or-miss trajectory. We examined the determinants of small plaque phenotype in two dengue virus (DENV) vaccine candidates, DENV-3 PGMK30FRhL3, which produced acute febrile illness in vaccine recipients, and DENV-2 PDK53, which has a good clinical safety profile. The reasons behind the failure of PGMK30FRhL3 during phase 1 clinical trial, despite meeting the empirically derived criteria of attenuation, have never been systematically investigated. Using in vitro, in vivo and functional genomics approaches, we examined infections by the vaccine and wild-type DENVs, in order to ascertain the different determinants of plaque size. We show that PGMK30FRhL3 produces small plaques on BHK-21 cells due to its slow in vitro growth rate. In contrast, PDK53 replicates rapidly, but is unable to evade antiviral responses that constrain its spread hence also giving rise to small plaques. Therefore, at least two different molecular mechanisms govern the plaque phenotype; determining which mechanism operates to constrain plaque size may be more informative on the safety of live-attenuated vaccines.
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