ArticleJournal of virology2011
Activation of the alphavirus spike protein is suppressed by bound E3.
Article in Journal of virology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 45 citations in OpenAlex.
- Current status on encephalitic alphavirus vaccines development: Advances, challenges, and global health perspectives.Infectious medicine · 2026Review
- Venezuelan equine encephalitis virus: novel live-attenuated vaccines for inducing complete protective immunity.Npj viruses · 2026Review
- FromImmune network · 2026Review
- Neutralizing antibodies against Chikungunya virus and structural elucidation of their mechanism of action.Nature communications · 2025Article
- A Review of the Biology of Chikungunya Virus Highlighting the Development of Current Novel Therapeutic and Prevention Approaches.Pathogens (Basel, Switzerland) · 2025Review
- Global Transmission and Evolution of Chikungunya Virus: Origins, Adaptive Mutations, and Intercontinental Spread of the Three Genotypes.Transboundary and emerging diseases · 2025Article
- Pathogenicity and virulence of chikungunya virus.Virulence · 2024Review
- A molecular understanding of alphavirus entry and antibody protection.Nature reviews. Microbiology · 2023Review
- Positive-strand RNA viruses-a Keystone Symposia report.Annals of the New York Academy of Sciences · 2023Article
- Cryo-EM structures of alphavirus conformational intermediates in low pH-triggered prefusion states.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Mutations at the Alphavirus E1'-E2 Interdimer Interface Have Host-Specific Phenotypes.Journal of virology · 2022Article
- The Structural Biology of Eastern Equine Encephalitis Virus, an Emerging Viral Threat.Pathogens (Basel, Switzerland) · 2021Review
- Cryo-EM structure of the mature and infective Mayaro virus at 4.4 Å resolution reveals features of arthritogenic alphaviruses.Nature communications · 2021Article
- Cathepsin L plays a key role in SARS-CoV-2 infection in humans and humanized mice and is a promising target for new drug development.Signal transduction and targeted therapy · 2021Article
- A molecular understanding of alphavirus entry.PLoS pathogens · 2020Review
- Anti-Chikungunya Virus Monoclonal Antibody That Inhibits Viral Fusion and Release.Journal of virology · 2020Article
- Human monoclonal antibodies against chikungunya virus target multiple distinct epitopes in the E1 and E2 glycoproteins.PLoS pathogens · 2019Article
- Molecular characteristics and replication mechanism of dengue, zika and chikungunya arboviruses, and their treatments with natural extracts from plants: An updated review.EXCLI journal · 2019Review
- Implication for alphavirus host-cell entry and assembly indicated by a 3.5Å resolution cryo-EM structure.Nature communications · 2018Article
- Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Alphaviruses are taken up into the endosome of the cell, where acidic conditions activate the spikes for membrane fusion. This involves dissociation of the three E2-E1 heterodimers of the spike and E1 interaction with the target membrane as a homotrimer. The biosynthesis of the heterodimer as a pH-resistant p62-E1 precursor appeared to solve the problem of premature activation in the late and acidic parts of the biosynthetic transport pathway in the cell. However, p62 cleavage into E2 and E3 by furin occurs before the spike has left the acidic compartments, accentuating the problem. In this work, we used a furin-resistant Semliki Forest virus (SFV) mutant, SFV(SQL), to study the role of E3 in spike activation. The cleavage was reconstituted with proteinase K in vitro using free virus or spikes on SFV(SQL)-infected cells. We found that E3 association with the spikes was pH dependent, requiring acidic conditions, and that the bound E3 suppressed spike activation. This was shown in an in vitro spike activation assay monitoring E1 trimer formation with liposomes and a fusion-from-within assay with infected cells. Furthermore, the wild type, SFV(wt), was found to bind significant amounts of E3, especially if produced in dense cultures, which lowered the pH of the culture medium. This E3 also suppressed spike activation. The results suggest that furin-cleaved E3 continues to protect the spike from premature activation in acidic compartments of the cell and that its release in the neutral extracellular space primes the spike for low-pH activation.
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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.