ArticlePLoS pathogens2010
In vitro and in vivo studies identify important features of dengue virus pr-E protein interactions.
Article in PLoS pathogens, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 1 of them a synthesis that pooled it.
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Who cites it
47 citing papers in PubMed, 1 synthesis or guideline pooled it, 95 citations in OpenAlex.
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- Association of intermediate monocytes with dengue severity among the pediatric population of Odisha, India.Scientific reports · 2025Article
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- Gut symbiont-derived sphingosine modulates vector competence in Aedes mosquitoes.Nature communications · 2024Article
- Recent advances in the study of zika virus structure, drug targets, and inhibitors.Frontiers in pharmacology · 2024Review
- Zika virus M protein latches and locks the E protein from transitioning to an immature state after prM cleavage.Npj viruses · 2023Article
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- prM-reactive antibodies reveal a role for partially mature virions in dengue virus pathogenesis.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Styrylpyrone Derivative (SPD) Extracted fromMolecules (Basel, Switzerland) · 2022Article
- Evolution and activation mechanism of the flavivirus class II membrane-fusion machinery.Nature communications · 2022Article
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- A Genome-Wide CRISPR-Cas9 Screen Identifies the Dolichol-Phosphate Mannose Synthase Complex as a Host Dependency Factor for Dengue Virus Infection.Journal of virology · 2020Article
- Structure-guided paradigm shifts in flavivirus assembly and maturation mechanisms.Advances in virus research · 2020Review
- Neutralization of Acidic Intracellular Vesicles by Niclosamide Inhibits Multiple Steps of the Dengue Virus Life Cycle In Vitro.Scientific reports · 2019Article
- Mechanism of Tetherin Inhibition of Alphavirus Release.Journal of virology · 2019Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Flaviviruses bud into the endoplasmic reticulum and are transported through the secretory pathway, where the mildly acidic environment triggers particle rearrangement and allows furin processing of the prM protein to pr and M. The peripheral pr peptide remains bound to virus at low pH and inhibits virus-membrane interaction. Upon exocytosis, the release of pr at neutral pH completes virus maturation to an infectious particle. Together this evidence suggests that pr may shield the flavivirus fusion protein E from the low pH environment of the exocytic pathway. Here we developed an in vitro system to reconstitute the interaction of dengue virus (DENV) pr with soluble truncated E proteins. At low pH recombinant pr bound to both monomeric and dimeric forms of E and blocked their membrane insertion. Exogenous pr interacted with mature infectious DENV and specifically inhibited virus fusion and infection. Alanine substitution of E H244, a highly conserved histidine residue in the pr-E interface, blocked pr-E interaction and reduced release of DENV virus-like particles. Folding, membrane insertion and trimerization of the H244A mutant E protein were preserved, and particle release could be partially rescued by neutralization of the low pH of the secretory pathway. Thus, pr acts to silence flavivirus fusion activity during virus secretion, and this function can be separated from the chaperone activity of prM. The sequence conservation of key residues involved in the flavivirus pr-E interaction suggests that this protein-protein interface may be a useful target for broad-spectrum inhibitors.
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