ArticleProceedings of the National Academy of Sciences of the United States of America2015
Structural and biochemical studies of HCMV gH/gL/gO and Pentamer reveal mutually exclusive cell entry complexes.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 107 papers.
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Who cites it
107 citing papers in PubMed.
- Integrin β3 α2,6-sialylation by the sialyltransferase ST6Gal1 promotes human cytomegalovirus entry into fibroblasts.Virulence · 2026Article
- Site-specific and global glycan analysis of the human cytomegalovirus pentameric glycoprotein by high resolution mass spectrometry.Glycobiology · 2026Article
- Mapping the monoclonal antibody landscape of human cytomegalovirus.Journal of virology · 2026Review
- A promising endeavor against human cytomegalovirus: Predominant epitopes-based recombinant subunit vaccine RHVirulence · 2025Article
- Eph receptor tyrosine kinases are functional entry receptors for murine gammaherpesvirus 68.PLoS pathogens · 2025Article
- Virion proteomics of genetically intact HCMV reveals a regulator of envelope glycoprotein composition that protects against humoral immunity.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- The GATE glycoprotein complex enhances human cytomegalovirus entry in endothelial cells.Nature microbiology · 2025Article
- Precision engineering of human cytomegalovirus without BAC constraints: a Sendai virus-delivered CRISPR/Cas9 approach.The Journal of general virology · 2025Article
- Small glycomimetic antagonists of the cytomegalovirus glycoprotein UL141 prevent binding to TRAIL death receptor.The Journal of biological chemistry · 2025Article
- The pentameric complex is not required for congenital CMV transmission in seronegative rhesus macaques.Science translational medicine · 2025Article
- Multi-Antigen Elephant Endotheliotropic Herpesvirus (EEHV) mRNA Vaccine Induces Humoral and Cell-Mediated Responses in Mice.Vaccines · 2024Article
- A broadly neutralizing human monoclonal antibody generated from transgenic mice immunized with HCMV particles limits virus infection and proliferation.Journal of virology · 2024Article
- Characterization of humoral and cellular immunologic responses to an mRNA-based human cytomegalovirus vaccine from a phase 1 trial of healthy adults.Journal of virology · 2024Article
- Virus-Induced Cell Fusion and Syncytia Formation.Results and problems in cell differentiation · 2024Article
- Article
- Neutralization Epitopes in Trimer and Pentamer Complexes Recognized by Potent Cytomegalovirus-Neutralizing Human Monoclonal Antibodies.Microbiology spectrum · 2022Article
- Virus-Associated Nephropathies: A Narrative Review.International journal of molecular sciences · 2022Review
- Horizontal Transmission of Cytomegalovirus in a Rhesus Model Despite High-Level, Vaccine-Elicited Neutralizing Antibody and T-Cell Responses.The Journal of infectious diseases · 2022Article
- Antibodies to combat viral infections: development strategies and progress.Nature reviews. Drug discovery · 2022Review
- Article
47 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors.
Funding
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Abstract
Human cytomegalovirus (HCMV) is a major cause of morbidity and mortality in transplant patients and the leading viral cause of birth defects after congenital infection. The glycoprotein complexes gH/gL/gO and gH/gL/UL128/UL130/UL131A (Pentamer) are key targets of the human humoral response against HCMV and are required for HCMV entry into fibroblasts and endothelial/epithelial cells, respectively. We expressed and characterized soluble forms of gH/gL, gH/gL/gO, and Pentamer. Mass spectrometry and mutagenesis analysis revealed that gL-Cys144 forms disulfide bonds with gO-Cys351 in gH/gL/gO and with UL128-Cys162 in the Pentamer. Notably, Pentamer harboring the UL128-Cys162Ser/gL-Cys144Ser mutations had impaired syncytia formation and reduced interference of HCMV entry into epithelial cells. Electron microscopy analysis showed that HCMV gH/gL resembles HSV gH/gL and that gO and UL128/UL130/UL131A bind to the same site at the gH/gL N terminus. These data are consistent with gH/gL/gO and Pentamer forming mutually exclusive cell entry complexes and reveal the overall location of gH/gL-, gH/gL/gO-, and Pentamer-specific neutralizing antibody binding sites. Our results provide, to our knowledge, the first structural view of gH/gL/gO and Pentamer supporting the development of vaccines and antibody therapeutics against HCMV.
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