ArticleJournal of virology2013
A key interaction between the alphavirus envelope proteins responsible for initial dimer dissociation during fusion.
Article in Journal of virology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 35 citations in OpenAlex.
- Article
- FromImmune network · 2026Review
- Getah Virus in Review: An Emerging Zoonotic Arbovirus.Transboundary and emerging diseases · 2026Review
- A Review of the Biology of Chikungunya Virus Highlighting the Development of Current Novel Therapeutic and Prevention Approaches.Pathogens (Basel, Switzerland) · 2025Review
- Changes in the chikungunya virus E1 glycoprotein domain II and hinge influence E2 conformation, infectivity, and virus-receptor interactions.Journal of virology · 2024Article
- Species-specific MARCO-alphavirus interactions dictate chikungunya virus viremia.Cell reports · 2023Article
- A high-throughput screening assay to identify inhibitory antibodies targeting alphavirus release.Virology journal · 2022Article
- Two Conserved Phenylalanine Residues in the E1 Fusion Loop of Alphaviruses Are Essential for Viral Infectivity.Journal of virology · 2022Article
- Structural Insights into Alphavirus Assembly Revealed by the Cryo-EM Structure of Getah Virus.Viruses · 2022Article
- The Structural Biology of Eastern Equine Encephalitis Virus, an Emerging Viral Threat.Pathogens (Basel, Switzerland) · 2021Review
- Overview on Chikungunya Virus Infection: From Epidemiology to State-of-the-Art Experimental Models.Frontiers in microbiology · 2021Review
- Acidic pH-Induced Conformational Changes in Chikungunya Virus Fusion Protein E1: a Spring-Twisted Region in the Domain I-III Linker Acts as a Hinge Point for Swiveling Motion of Domains.Journal of virology · 2020Article
- Human monoclonal antibodies against Ross River virus target epitopes within the E2 protein and protect against disease.PLoS pathogens · 2020Article
- Prediction of MAYV peptide antigens for immunodiagnostic tests by immunoinformatics and molecular dynamics simulations.Scientific reports · 2019Article
- The effect of amantadine on an ion channel protein from Chikungunya virus.PLoS neglected tropical diseases · 2019Article
- Review
- AnmBio · 2017Article
- Article
- Early Events in Chikungunya Virus Infection-From Virus Cell Binding to Membrane Fusion.Viruses · 2015Review
- Residue-level resolution of alphavirus envelope protein interactions in pH-dependent fusion.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Alphaviruses such as Semliki Forest virus (SFV) are enveloped viruses whose surface is covered by an organized lattice composed of trimers of E2-E1 heterodimers. The E1 envelope protein, a class II fusion protein, contains the hydrophobic fusion loop and refolds to drive virus fusion with the endosome membrane. The E2 protein is synthesized as a precursor p62, whose processing by furin primes the heterodimer for dissociation during virus entry. Dissociation of the E2-E1 heterodimer is an essential step during low-pH-triggered fusion, while the dissociation of the immature p62-E1 dimer is relatively pH resistant. Previous structural studies described an "acid-sensitive region" in E2 that becomes disordered at low pH. Within this region, the conserved E2 H170 is in position to form a hydrogen bond with the underlying E1 S57. Here we experimentally tested the role of this interaction in regulating dimer dissociation in mature and immature virus. Alanine substitutions of E1 S57 and E2 H170 destabilized the heterodimer and produced a higher pH threshold for exposure of the E1 fusion loop and for fusion of the immature virus. E1 S57K or S57D mutations were lethal and caused transport and assembly defects that were partially abrogated by neutralization of the exocytic pathway. The lethal phenotype of E1 S57K was rescued by second-site mutations at E2 H170/M171. Together, our results define a key role for the E1 S57-E2 H170 interaction in dimer stability and the pH dependence of fusion and provide evidence for stepwise dissociation of the E2-E1 dimer at low pH.
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Registered trials
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