ArticleJournal of virology2013
The large groove found in the gH/gL structure is an important functional domain for Epstein-Barr virus 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 28 papers.
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Who cites it
28 citing papers in PubMed, 36 citations in OpenAlex.
- A Neutralizing Antibody Targeting gH Provides Potent Protection against EBV ChallengeJournal of virology · 2022Article
- A potent and protective human neutralizing antibody targeting a novel vulnerable site of Epstein-Barr virus.Nature communications · 2021Article
- A conditionally replication-defective cytomegalovirus vaccine elicits potent and diverse functional monoclonal antibodies in a phase I clinical trial.NPJ vaccines · 2021Article
- Review
- Epstein-Barr Virus gH/gL and Kaposi's Sarcoma-Associated Herpesvirus gH/gL Bind to Different Sites on EphA2 To Trigger Fusion.Journal of virology · 2020Article
- Epstein-Barr virus circRNAome as host miRNA sponge regulates virus infection, cell cycle, and oncogenesis.Bioengineered · 2019Article
- Epithelial cell infection by Epstein-Barr virus.FEMS microbiology reviews · 2019Article
- An Antibody Targeting the Fusion Machinery Neutralizes Dual-Tropic Infection and Defines a Site of Vulnerability on Epstein-Barr Virus.Immunity · 2018Article
- Ephrin receptor A2 is a functional entry receptor for Epstein-Barr virus.Nature microbiology · 2018Article
- Inhibition of EBV-mediated membrane fusion by anti-gHgL antibodies.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Structural basis for Epstein-Barr virus host cell tropism mediated by gp42 and gHgL entry glycoproteins.Nature communications · 2016Article
- Varicella-Zoster Virus Glycoproteins: Entry, Replication, and Pathogenesis.Current clinical microbiology reports · 2016Article
- Article
- gH/gL supercomplexes at early stages of herpesvirus entry.Current opinion in virology · 2016Review
- Structural and Mechanistic Insights into the Tropism of Epstein-Barr Virus.Molecules and cells · 2016Review
- Mutations in Pseudorabies Virus Glycoproteins gB, gD, and gH Functionally Compensate for the Absence of gL.Journal of virology · 2015Article
- Comparative Mutagenesis of Pseudorabies Virus and Epstein-Barr Virus gH Identifies a Structural Determinant within Domain III of gH Required for Surface Expression and Entry Function.Journal of virology · 2015Article
- A site of varicella-zoster virus vulnerability identified by structural studies of neutralizing antibodies bound to the glycoprotein complex gHgL.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Structural and biochemical studies of HCMV gH/gL/gO and Pentamer reveal mutually exclusive cell entry complexes.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Article
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Epstein-Barr virus (EBV) mediates viral entry into cells using four glycoproteins-gB, the gH/gL complex, and gp42-and fusion is cell type specific. gB and gH/gL are required for epithelial cell fusion; B cell fusion also requires gp42. To investigate functional domains within the gH/gL structure, we constructed site-directed EBV gH/gL mutants with alterations of residues located in a large groove that separates domain I (D-I) from domain II (D-II) within the gH/gL structure. We found that substitution of alanine for leucine 207 reduces both epithelial and B cell fusion and is accompanied by reduced gp42 binding. We also observed that substitution of alanine for arginine 152, histidine 154, or threonine 174 reduces fusion with epithelial cells but not with B cells. To test whether flexibility of the region between D-I and D-II of gH/gL could be important for membrane fusion activity and to allow potential interactions across the D-I/D-II groove, we mutated D-I amino acids V47, P48, and G49 to cysteine, allowing novel intersubunit disulfide bonds to form with the free C153 located in D-II. We found that the G49C mutant, predicted to bridge D-I and D-II with C153 of gH/gL, had normal B cell fusion activity but reduced epithelial cell fusion activity, which was partially restored by treatment with dithiothreitol. We conclude that structural rearrangements and/or interactions across the D-I/D-II groove of gH/gL are required for fusion with epithelial cells but not for fusion with B cells.
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Registered trials
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.