ArticleJournal of virology2020
Polymorphisms in Human Cytomegalovirus Glycoprotein O (gO) Exert Epistatic Influences on Cell-Free and Cell-to-Cell Spread and Antibody Neutralization on gH Epitopes.
Article in Journal of virology, 2020. 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, 39 citations in OpenAlex.
- Human herpesvirus evasion of humoral immunity and implications for vaccine development.Nature reviews. Microbiology · 2026Review
- Knockout of key receptors (PDGFRA and NRP2) in the guinea pig model blocks direct and endocytic pathways of CMV cell entry.The Journal of general virology · 2026Article
- Interstrain recombinants of human cytomegalovirus uncouple glycoprotein display, virion infectivity, and spread characteristics.Journal of virology · 2026Article
- Article
- 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
- Interstrain Recombinants of Human Cytomegalovirus Reveal Complex Genetic Correlates and Epistasis Influencing Glycoprotein Display, Virion Infectivity and Spread Characteristics.bioRxiv : the preprint server for biology · 2025Article
- Identification of the human cytomegalovirus gHgLgO trimer as the central player in virion infectivity.PLoS pathogens · 2025Article
- Human cytomegalovirus gH/gL/gO binding to PDGFRα provides a regulatory signal activating the fusion protein gB that can be blocked by neutralizing antibodies.Journal of virology · 2025Article
- Cytomegalovirus Genetic Diversity and Evolution: Insights into Genotypes and Their Role in Viral Pathogenesis.Pathogens (Basel, Switzerland) · 2025Review
- A broadly neutralizing human monoclonal antibody generated from transgenic mice immunized with HCMV particles limits virus infection and proliferation.Journal of virology · 2024Article
- Decoding human cytomegalovirus for the development of innovative diagnostics to detect congenital infection.Pediatric research · 2024Review
- Human cytomegalovirus and neonatal infection.Current research in microbial sciences · 2024Review
- Review
- A Virus Genetic System to Analyze the Fusogenicity of Human Cytomegalovirus Glycoprotein B Variants.Viruses · 2023Article
- Fibroblast, Epithelial and Endothelial Cell-Derived Human Cytomegalovirus Strains Display Distinct Neutralizing Antibody Responses and Varying Levels of gH/gL Complexes.International journal of molecular sciences · 2023Article
- Intermittent bulk release of human cytomegalovirus.PLoS pathogens · 2022Article
- Article
- Development of broadly neutralizing antibodies targeting the cytomegalovirus subdominant antigen gH.Communications biology · 2022Article
- Cross Strain Protection against Cytomegalovirus Reduces DISC Vaccine Efficacy against CMV in the Guinea Pig Model.Viruses · 2022Article
- Review
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Human cytomegalovirus (HCMV) glycoproteins H and L (gH/gL) can be bound by either gO or the UL128 to UL131 proteins (referred to here as UL128-131) to form complexes that facilitate entry and spread, and the complexes formed are important targets of neutralizing antibodies. Strains of HCMV vary considerably in the levels of gH/gL/gO and gH/gL/UL128-131, and this can impact infectivity and cell tropism. In this study, we investigated how natural interstrain variation in the amino acid sequence of gO influences the biology of HCMV. Heterologous gO recombinants were constructed in which 6 of the 8 alleles or genotypes (GT) of gO were analyzed in the backgrounds of strains TR and Merlin (ME). The levels of gH/gL complexes were not affected, but there were impacts on entry, spread, and neutralization by anti-gH antibodies. AD169 (AD) gO (GT1a) [referred to here as ADgO(GT1a)] drastically reduced cell-free infectivity of both strains on fibroblasts and epithelial cells. PHgO(GT2a) increased cell-free infectivity of TR in both cell types, but spread in fibroblasts was impaired. In contrast, spread of ME in both cell types was enhanced by Towne (TN) gO (GT4), despite similar cell-free infectivity. TR expressing TNgO(GT4) was resistant to neutralization by anti-gH antibodies AP86 and 14-4b, whereas ADgO(GT1a) conferred resistance to 14-4b but enhanced neutralization by AP86. Conversely, ME expressing ADgO(GT1a) was more resistant to 14-4b. These results suggest that (i) there are mechanistically distinct roles for gH/gL/gO in cell-free and cell-to-cell spread, (ii) gO isoforms can differentially shield the virus from neutralizing antibodies, and (iii) effects of gO polymorphisms are epistatically dependent on other variable loci.
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