ArticleJournal of virology2013
The role of E3 in pH protection during alphavirus assembly and exit.
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 54 papers, 1 of them a synthesis that pooled it.
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Who cites it
54 citing papers in PubMed, 1 synthesis or guideline pooled it, 76 citations in OpenAlex.
- The life cycle of the alphaviruses: From an antiviral perspective.Antiviral research · 2023Pooled it
- Research progress on the role of host factors in Chikungunya virus infection and intervention strategies.Virulence · 2026Review
- Alphavirus replicase and regulatory RNA elements in host interactions and viral vector engineering.Journal of virology · 2026Review
- Current status on encephalitic alphavirus vaccines development: Advances, challenges, and global health perspectives.Infectious medicine · 2026Review
- Recent advances in antiviral drugs for Chikungunya virus (CHIKV): Targets, mechanisms, and development strategies.Acta pharmaceutica Sinica. B · 2026Review
- Article
- FromImmune network · 2026Review
- Unraveling chikungunya's viral tapestry through molecular mechanisms and clinical insights.Infectious diseases & immunity · 2026Review
- Neutralizing antibodies against Chikungunya virus and structural elucidation of their mechanism of action.Nature communications · 2025Article
- Beyond Processing: Furin as a Central Hub in Viral Pathogenesis and Genetic Susceptibility.Biomolecules · 2025Review
- A Review of the Biology of Chikungunya Virus Highlighting the Development of Current Novel Therapeutic and Prevention Approaches.Pathogens (Basel, Switzerland) · 2025Review
- Determinants of human versus mosquito cell entry by the Chikungunya virus envelope proteins.bioRxiv : the preprint server for biology · 2025Article
- VSV-CHIKV activates antitumor immunity by inducing pyroptosis in a melanoma model.Discover oncology · 2025Article
- Interaction of the endogenous antibody response with activating FcγRs enhance control of Mayaro virus through monocytes.PLoS pathogens · 2025Article
- Current perspectives on alphavirus encapsidation, assembly and budding.Frontiers in cellular and infection microbiology · 2025Review
- Heterogeneous Ribonucleoprotein K Is a Host Regulatory Factor of Chikungunya Virus Replication in Astrocytes.Viruses · 2024Article
- Chikungunya virus E2 B domain nanoparticle immunogen elicits homotypic neutralizing antibody in mice.Vaccine · 2024Article
- Pathogenicity and virulence of chikungunya virus.Virulence · 2024Review
- Activating FcγRs on monocytes are necessary for optimal Mayaro virus clearance.bioRxiv : the preprint server for biology · 2024Article
- Development and application of a colloidal-gold immunochromatographic strip for detecting Getah virus antibodies.Applied microbiology and biotechnology · 2024Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Alphaviruses are small enveloped viruses whose surface is covered by spikes composed of trimers of E2/E1 glycoprotein heterodimers. During virus entry, the E2/E1 dimer dissociates within the acidic endosomal environment, freeing the E1 protein to mediate fusion of the viral and endosome membranes. E2 is synthesized as a precursor, p62, which is cleaved by furin in the late secretory pathway to produce mature E2 and a small peripheral glycoprotein, E3. The immature p62/E1 dimer is acid resistant, but since p62 is cleaved before exit from the acidic secretory pathway, low pH-dependent binding of E3 to the spike complex is believed to prevent premature fusion. Based on analysis of the structure of the Chikungunya virus E3/E2/E1 complex, we hypothesized that interactions of E3 residues Y47 and Y48 with E2 are important in this binding. We then directly tested the in vivo role of E3 in pH protection by alanine substitutions of E3 Y47 and Y48 (Y47/48A) in Semliki Forest virus. The mutant was nonviable and was blocked in E1 transport to the plasma membrane and virus production. Although the Y47/48A mutant initially formed the p62/E1 heterodimer, the dimer dissociated during transport through the secretory pathway. Neutralization of the pH in the secretory pathway successfully rescued dimer association, E1 transport, and infectious particle production. Further mutagenesis identified the critical contact as the cation-π interaction of E3 Y47 with E2. Thus, E3 mediates pH protection of E1 during virus biogenesis via interactions strongly dependent on Y47 at the E3-E2 interface.
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Registered trials
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