ArticleProceedings of the National Academy of Sciences of the United States of America2013
An immunoreceptor tyrosine-based inhibition motif in varicella-zoster virus glycoprotein B regulates cell fusion and skin pathogenesis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 43 citations in OpenAlex.
- Varicella Zoster Virus Infection: Clinical Features, Molecular Pathogenesis, Treatment, and Prevention.MedComm · 2026Review
- Biological relevance ofMicrobiology and molecular biology reviews : MMBR · 2025Review
- Article
- The Autonomous Fusion Activity of Human Cytomegalovirus Glycoprotein B Is Regulated by Its Carboxy-Terminal Domain.Viruses · 2024Article
- Targeted mutagenesis of the herpesvirus fusogen central helix captures transition states.Nature communications · 2023Article
- Creating the "Dew Drop on a Rose Petal": the Molecular Pathogenesis of Varicella-Zoster Virus Skin Lesions.Microbiology and molecular biology reviews : MMBR · 2023Review
- The Structures and Functions of VZV Glycoproteins.Current topics in microbiology and immunology · 2023Article
- Virus-induced interference as a means for accelerating fitness-based selection of cyprinid herpesvirus 3 single-nucleotide variantsVirus evolution · 2023Article
- MAIA, Fc receptor-like 3, supersedes JUNO as IZUMO1 receptor during human fertilization.Science advances · 2022Article
- Article
- Review
- Review
- Review
- The structural basis of herpesvirus entry.Nature reviews. Microbiology · 2021Review
- Entry of Alphaherpesviruses.Current issues in molecular biology · 2021Review
- The N-terminus of varicella-zoster virus glycoprotein B has a functional role in fusion.PLoS pathogens · 2021Article
- Varicella-zoster virus: molecular controls of cell fusion-dependent pathogenesis.Biochemical Society transactions · 2020Review
- Calcineurin phosphatase activity regulates Varicella-Zoster Virus induced cell-cell fusion.PLoS pathogens · 2020Article
- A glycoprotein B-neutralizing antibody structure at 2.8 Å uncovers a critical domain for herpesvirus fusion initiation.Nature communications · 2020Article
- Skin Viral Infections: Host Antiviral Innate Immunity and Viral Immune Evasion.Frontiers in immunology · 2020Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Herpesvirus entry functions of the conserved glycoproteins gB and gH-gL have been delineated, but their role in regulating cell-cell fusion is poorly understood. Varicella-zoster virus (VZV) infection provides a valuable model for investigating cell-cell fusion because of the importance of this process for pathogenesis in human skin and sensory ganglia. The present study identifies a canonical immunoreceptor tyrosine-based inhibition motif (ITIM) in the gB cytoplasmic domain (gBcyt) and demonstrates that the gBcyt is a tyrosine kinase substrate. Orbitrap mass spectrometry confirmed that Y881, central to the ITIM, is phosphorylated. To determine whether the gBcyt ITIM regulates gB/gH-gL-induced cell-cell fusion in vitro, tyrosine residues Y881 and Y920 in the gBcyt were substituted with phenylalanine separately or together. Recombinant viruses with these substitutions were generated to establish their effects on syncytia formation in replication in vitro and in the human skin xenograft model of VZV pathogenesis. The Y881F substitution caused significantly increased cell-cell fusion despite reduced cell-surface gB. Importantly, the Y881F or Y881/920F substitutions in VZV caused aggressive syncytia formation, reducing cell-cell spread. These in vitro effects of aggressive syncytia formation translated to severely impaired skin infection in vivo. In contrast, the Y920F substitution did not affect virus replication in vitro or in vivo. These observations suggest that gB modulates cell-cell fusion via an ITIM-mediated Y881 phosphorylation-dependent mechanism, supporting a unique concept that intracellular signaling through this gBcyt motif regulates VZV syncytia formation and is essential for skin pathogenesis.
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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.