Rhesus Cytomegalovirus-encoded Fcγ-binding glycoproteins facilitate viral evasion from IgG-mediated humoral immunity
Abstract Human cytomegalovirus (HCMV) encodes four viral Fc-gamma receptors (vFcγRs) that counteract antibody-mediated activation in vitro, but their role in infection and pathogenesis is unknown. To examine their in vivo function in an animal model evolutionarily closely related to humans, we ident...
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Nature Portfolio
2025-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-56419-3 |
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| author | Claire E. Otero Sophia Petkova Martin Ebermann Husam Taher Nessy John Katja Hoffmann Angel Davalos Matilda J. Moström Roxanne M. Gilbride Courtney R. Papen Aaron Barber-Axthelm Elizabeth A. Scheef Richard Barfield Lesli M. Sprehe Savannah Kendall Tabitha D. Manuel Teresa Beechwood Linh Khanh Nguyen Nathan H. Vande Burgt Cliburn Chan Michael Denton Zachary J. Streblow Daniel N. Streblow Alice F. Tarantal Scott G. Hansen Amitinder Kaur Sallie Permar Klaus Früh Hartmut Hengel Daniel Malouli Philipp Kolb |
| author_facet | Claire E. Otero Sophia Petkova Martin Ebermann Husam Taher Nessy John Katja Hoffmann Angel Davalos Matilda J. Moström Roxanne M. Gilbride Courtney R. Papen Aaron Barber-Axthelm Elizabeth A. Scheef Richard Barfield Lesli M. Sprehe Savannah Kendall Tabitha D. Manuel Teresa Beechwood Linh Khanh Nguyen Nathan H. Vande Burgt Cliburn Chan Michael Denton Zachary J. Streblow Daniel N. Streblow Alice F. Tarantal Scott G. Hansen Amitinder Kaur Sallie Permar Klaus Früh Hartmut Hengel Daniel Malouli Philipp Kolb |
| author_sort | Claire E. Otero |
| collection | DOAJ |
| description | Abstract Human cytomegalovirus (HCMV) encodes four viral Fc-gamma receptors (vFcγRs) that counteract antibody-mediated activation in vitro, but their role in infection and pathogenesis is unknown. To examine their in vivo function in an animal model evolutionarily closely related to humans, we identified and characterized Rh05, Rh152/151 and Rh173 as the complete set of vFcγRs encoded by rhesus CMV (RhCMV). Each one of these proteins displays functional similarities to their prospective HCMV orthologs with respect to antagonizing host FcγR activation in vitro. When RhCMV-naïve male rhesus macaques were infected with vFcγR-deleted RhCMV, peak plasma DNAemia levels and anti-RhCMV antibody responses were comparable to wildtype infections of both male and female animals. However, the duration of plasma DNAemia was significantly shortened in immunocompetent, but not in CD4 + T cell-depleted animals. Since vFcγRs were not required for superinfection of rhesus macaques, we conclude that these proteins can prolong lytic replication during primary infection by evading virus-specific adaptive immune responses, particularly antibodies. |
| format | Article |
| id | doaj-art-0e094a48e7744c379092ad64f4958019 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-0e094a48e7744c379092ad64f49580192025-02-02T12:31:42ZengNature PortfolioNature Communications2041-17232025-01-0116111610.1038/s41467-025-56419-3Rhesus Cytomegalovirus-encoded Fcγ-binding glycoproteins facilitate viral evasion from IgG-mediated humoral immunityClaire E. Otero0Sophia Petkova1Martin Ebermann2Husam Taher3Nessy John4Katja Hoffmann5Angel Davalos6Matilda J. Moström7Roxanne M. Gilbride8Courtney R. Papen9Aaron Barber-Axthelm10Elizabeth A. Scheef11Richard Barfield12Lesli M. Sprehe13Savannah Kendall14Tabitha D. Manuel15Teresa Beechwood16Linh Khanh Nguyen17Nathan H. Vande Burgt18Cliburn Chan19Michael Denton20Zachary J. Streblow21Daniel N. Streblow22Alice F. Tarantal23Scott G. Hansen24Amitinder Kaur25Sallie Permar26Klaus Früh27Hartmut Hengel28Daniel Malouli29Philipp Kolb30Department of Pediatrics, Weill Cornell MedicineInstitute of Virology, Medical Center, Faculty of Medicine, University of FreiburgInstitute of Virology, Medical Center, Faculty of Medicine, University of FreiburgVaccine and Gene Therapy Institute, Oregon Health and Science UniversityVaccine and Gene Therapy Institute, Oregon Health and Science UniversityInstitute of Virology, Medical Center, Faculty of Medicine, University of FreiburgDepartment of Biostatistics and Bioinformatics, Duke UniversityTulane National Primate Research Center, Tulane UniversityVaccine and Gene Therapy Institute, Oregon Health and Science UniversityVaccine and Gene Therapy Institute, Oregon Health and Science UniversityVaccine and Gene Therapy Institute, Oregon Health and Science UniversityTulane National Primate Research Center, Tulane UniversityDepartment of Biostatistics and Bioinformatics, Duke UniversityTulane National Primate Research Center, Tulane UniversityTulane National Primate Research Center, Tulane UniversityTulane National Primate Research Center, Tulane UniversityVaccine and Gene Therapy Institute, Oregon Health and Science UniversityVaccine and Gene Therapy Institute, Oregon Health and Science UniversityVaccine and Gene Therapy Institute, Oregon Health and Science UniversityDepartment of Biostatistics and Bioinformatics, Duke UniversityVaccine and Gene Therapy Institute, Oregon Health and Science UniversityVaccine and Gene Therapy Institute, Oregon Health and Science UniversityVaccine and Gene Therapy Institute, Oregon Health and Science UniversityDepartments of Pediatrics and Cell Biology and Human Anatomy, School of Medicine, and California National Primate Research Center, University of CaliforniaVaccine and Gene Therapy Institute, Oregon Health and Science UniversityTulane National Primate Research Center, Tulane UniversityDepartment of Pediatrics, Weill Cornell MedicineVaccine and Gene Therapy Institute, Oregon Health and Science UniversityInstitute of Virology, Medical Center, Faculty of Medicine, University of FreiburgVaccine and Gene Therapy Institute, Oregon Health and Science UniversityInstitute of Virology, Medical Center, Faculty of Medicine, University of FreiburgAbstract Human cytomegalovirus (HCMV) encodes four viral Fc-gamma receptors (vFcγRs) that counteract antibody-mediated activation in vitro, but their role in infection and pathogenesis is unknown. To examine their in vivo function in an animal model evolutionarily closely related to humans, we identified and characterized Rh05, Rh152/151 and Rh173 as the complete set of vFcγRs encoded by rhesus CMV (RhCMV). Each one of these proteins displays functional similarities to their prospective HCMV orthologs with respect to antagonizing host FcγR activation in vitro. When RhCMV-naïve male rhesus macaques were infected with vFcγR-deleted RhCMV, peak plasma DNAemia levels and anti-RhCMV antibody responses were comparable to wildtype infections of both male and female animals. However, the duration of plasma DNAemia was significantly shortened in immunocompetent, but not in CD4 + T cell-depleted animals. Since vFcγRs were not required for superinfection of rhesus macaques, we conclude that these proteins can prolong lytic replication during primary infection by evading virus-specific adaptive immune responses, particularly antibodies.https://doi.org/10.1038/s41467-025-56419-3 |
| spellingShingle | Claire E. Otero Sophia Petkova Martin Ebermann Husam Taher Nessy John Katja Hoffmann Angel Davalos Matilda J. Moström Roxanne M. Gilbride Courtney R. Papen Aaron Barber-Axthelm Elizabeth A. Scheef Richard Barfield Lesli M. Sprehe Savannah Kendall Tabitha D. Manuel Teresa Beechwood Linh Khanh Nguyen Nathan H. Vande Burgt Cliburn Chan Michael Denton Zachary J. Streblow Daniel N. Streblow Alice F. Tarantal Scott G. Hansen Amitinder Kaur Sallie Permar Klaus Früh Hartmut Hengel Daniel Malouli Philipp Kolb Rhesus Cytomegalovirus-encoded Fcγ-binding glycoproteins facilitate viral evasion from IgG-mediated humoral immunity Nature Communications |
| title | Rhesus Cytomegalovirus-encoded Fcγ-binding glycoproteins facilitate viral evasion from IgG-mediated humoral immunity |
| title_full | Rhesus Cytomegalovirus-encoded Fcγ-binding glycoproteins facilitate viral evasion from IgG-mediated humoral immunity |
| title_fullStr | Rhesus Cytomegalovirus-encoded Fcγ-binding glycoproteins facilitate viral evasion from IgG-mediated humoral immunity |
| title_full_unstemmed | Rhesus Cytomegalovirus-encoded Fcγ-binding glycoproteins facilitate viral evasion from IgG-mediated humoral immunity |
| title_short | Rhesus Cytomegalovirus-encoded Fcγ-binding glycoproteins facilitate viral evasion from IgG-mediated humoral immunity |
| title_sort | rhesus cytomegalovirus encoded fcγ binding glycoproteins facilitate viral evasion from igg mediated humoral immunity |
| url | https://doi.org/10.1038/s41467-025-56419-3 |
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