ArticlePLoS pathogens2017
A single mutation in the envelope protein modulates flavivirus antigenicity, stability, and pathogenesis.
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 57 papers.
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Who cites it
57 citing papers in PubMed, 89 citations in OpenAlex.
- Computational approaches for flavivirus drug discovery: targeting structural and non-structural proteins.RSC medicinal chemistry · 2026Review
- Designing potent and immunogenic epitope based peptide vaccine against all serotypes of DENV via structural, physico-chemical and immunoinformatics-based approaches.Scientific reports · 2026Article
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- A single residue in the yellow fever virus envelope protein modulates virion architecture and antigenicity.Nature communications · 2025Article
- Rising temperatures contribute to West Nile virus diversification and increased transmission potential.Scientific reports · 2025Article
- Evolution of Zika virus inVirus evolution · 2025Article
- Comparative genomics and evolutionary analysis of dengue virus strains circulating in Pakistan.Virus genes · 2024Article
- UK mosquitoes are competent to transmit Usutu virus at native temperatures.One health (Amsterdam, Netherlands) · 2024Article
- Envelope domain III EJournal of virology · 2024Article
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- Identification of the flavivirus conserved residues in the envelope protein hinge region for the rational design of a candidate West Nile live-attenuated vaccine.NPJ vaccines · 2023Article
- Single B cell transcriptomics identifies multiple isotypes of broadly neutralizing antibodies against flaviviruses.PLoS pathogens · 2023Article
- Impact of structural dynamics on biological functions of flaviviruses.The FEBS journal · 2023Review
- Charge-changing point mutations in the E protein of tick-borne encephalitis virus.Archives of virology · 2023Article
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- PD1 CD44 antiviral peptide as an inhibitor of the protein-protein interaction in dengue virus invasion.Peptides · 2022Article
- Signaling events evoked by domain III of envelop glycoprotein of tick-borne encephalitis virus and West Nile virus in human brain microvascular endothelial cells.Scientific reports · 2022Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
The structural flexibility or 'breathing' of the envelope (E) protein of flaviviruses allows virions to sample an ensemble of conformations at equilibrium. The molecular basis and functional consequences of virus conformational dynamics are poorly understood. Here, we identified a single mutation at residue 198 (T198F) of the West Nile virus (WNV) E protein domain I-II hinge that regulates virus breathing. The T198F mutation resulted in a ~70-fold increase in sensitivity to neutralization by a monoclonal antibody targeting a cryptic epitope in the fusion loop. Increased exposure of this otherwise poorly accessible fusion loop epitope was accompanied by reduced virus stability in solution at physiological temperatures. Introduction of a mutation at the analogous residue of dengue virus (DENV), but not Zika virus (ZIKV), E protein also increased accessibility of the cryptic fusion loop epitope and decreased virus stability in solution, suggesting that this residue modulates the structural ensembles sampled by distinct flaviviruses at equilibrium in a context dependent manner. Although the T198F mutation did not substantially impair WNV growth kinetics in vitro, studies in mice revealed attenuation of WNV T198F infection. Overall, our study provides insight into the molecular basis and the in vitro and in vivo consequences of flavivirus breathing.
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