Human cytomegalovirus antagonizes activation of Fcγ receptors by distinct and synergizing modes of IgG manipulation
Human cytomegalovirus (HCMV) is endowed with multiple highly sophisticated immune evasion strategies. This includes the evasion from antibody mediated immune control by counteracting host Fc-gamma receptor (FcγR) mediated immune control mechanisms such as antibody-dependent cellular cytotoxicity (AD...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2021-03-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/63877 |
| _version_ | 1811180555998330880 |
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| author | Philipp Kolb Katja Hoffmann Annika Sievert Henrike Reinhard Eva Merce-Maldonado Vu Thuy Khanh Le-Trilling Anne Halenius Dominique Gütle Hartmut Hengel |
| author_facet | Philipp Kolb Katja Hoffmann Annika Sievert Henrike Reinhard Eva Merce-Maldonado Vu Thuy Khanh Le-Trilling Anne Halenius Dominique Gütle Hartmut Hengel |
| author_sort | Philipp Kolb |
| collection | DOAJ |
| description | Human cytomegalovirus (HCMV) is endowed with multiple highly sophisticated immune evasion strategies. This includes the evasion from antibody mediated immune control by counteracting host Fc-gamma receptor (FcγR) mediated immune control mechanisms such as antibody-dependent cellular cytotoxicity (ADCC). We have previously shown that HCMV avoids FcγR activation by concomitant expression of the viral Fc-gamma-binding glycoproteins (vFcγRs) gp34 and gp68. We now show that gp34 and gp68 bind IgG simultaneously at topologically different Fcγ sites and achieve efficient antagonization of host FcγR activation by distinct but synergizing mechanisms. While gp34 enhances immune complex internalization, gp68 acts as inhibitor of host FcγR binding to immune complexes. In doing so, gp68 induces Fcγ accessibility to gp34 and simultaneously limits host FcγR recognition. The synergy of gp34 and gp68 is compelled by the interfering influence of excessive non-immune IgG ligands and highlights conformational changes within the IgG globular chains critical for antibody effector function. |
| first_indexed | 2024-04-11T09:05:18Z |
| format | Article |
| id | doaj.art-afb9195809604dedb2682b7e1f408806 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-11T09:05:18Z |
| publishDate | 2021-03-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-afb9195809604dedb2682b7e1f4088062022-12-22T04:32:39ZengeLife Sciences Publications LtdeLife2050-084X2021-03-011010.7554/eLife.63877Human cytomegalovirus antagonizes activation of Fcγ receptors by distinct and synergizing modes of IgG manipulationPhilipp Kolb0https://orcid.org/0000-0001-7935-217XKatja Hoffmann1Annika Sievert2Henrike Reinhard3Eva Merce-Maldonado4Vu Thuy Khanh Le-Trilling5Anne Halenius6Dominique Gütle7Hartmut Hengel8https://orcid.org/0000-0002-3482-816XFaculty of Medicine, Albert-Ludwigs-University Freiburg, Freiburg, Germany; Institute of Virology, University Medical Center, Albert-Ludwigs-University Freiburg, Freiburg, GermanyFaculty of Medicine, Albert-Ludwigs-University Freiburg, Freiburg, Germany; Institute of Virology, University Medical Center, Albert-Ludwigs-University Freiburg, Freiburg, GermanyFaculty of Medicine, Albert-Ludwigs-University Freiburg, Freiburg, Germany; Institute of Virology, University Medical Center, Albert-Ludwigs-University Freiburg, Freiburg, GermanyInstitute of Virology, University Hospital Düsseldorf, Heinrich-Heine-University Düsseldorf, Düsseldorf, GermanyInstitute of Virology, University Hospital Düsseldorf, Heinrich-Heine-University Düsseldorf, Düsseldorf, GermanyInstitute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen, GermanyFaculty of Medicine, Albert-Ludwigs-University Freiburg, Freiburg, Germany; Institute of Virology, University Medical Center, Albert-Ludwigs-University Freiburg, Freiburg, GermanyFaculty of Medicine, Albert-Ludwigs-University Freiburg, Freiburg, Germany; Institute of Virology, University Medical Center, Albert-Ludwigs-University Freiburg, Freiburg, GermanyFaculty of Medicine, Albert-Ludwigs-University Freiburg, Freiburg, Germany; Institute of Virology, University Medical Center, Albert-Ludwigs-University Freiburg, Freiburg, GermanyHuman cytomegalovirus (HCMV) is endowed with multiple highly sophisticated immune evasion strategies. This includes the evasion from antibody mediated immune control by counteracting host Fc-gamma receptor (FcγR) mediated immune control mechanisms such as antibody-dependent cellular cytotoxicity (ADCC). We have previously shown that HCMV avoids FcγR activation by concomitant expression of the viral Fc-gamma-binding glycoproteins (vFcγRs) gp34 and gp68. We now show that gp34 and gp68 bind IgG simultaneously at topologically different Fcγ sites and achieve efficient antagonization of host FcγR activation by distinct but synergizing mechanisms. While gp34 enhances immune complex internalization, gp68 acts as inhibitor of host FcγR binding to immune complexes. In doing so, gp68 induces Fcγ accessibility to gp34 and simultaneously limits host FcγR recognition. The synergy of gp34 and gp68 is compelled by the interfering influence of excessive non-immune IgG ligands and highlights conformational changes within the IgG globular chains critical for antibody effector function.https://elifesciences.org/articles/63877cytomegalovirusimmunoglobulinfc receptorsnatural killer cellsimmune evasion |
| spellingShingle | Philipp Kolb Katja Hoffmann Annika Sievert Henrike Reinhard Eva Merce-Maldonado Vu Thuy Khanh Le-Trilling Anne Halenius Dominique Gütle Hartmut Hengel Human cytomegalovirus antagonizes activation of Fcγ receptors by distinct and synergizing modes of IgG manipulation eLife cytomegalovirus immunoglobulin fc receptors natural killer cells immune evasion |
| title | Human cytomegalovirus antagonizes activation of Fcγ receptors by distinct and synergizing modes of IgG manipulation |
| title_full | Human cytomegalovirus antagonizes activation of Fcγ receptors by distinct and synergizing modes of IgG manipulation |
| title_fullStr | Human cytomegalovirus antagonizes activation of Fcγ receptors by distinct and synergizing modes of IgG manipulation |
| title_full_unstemmed | Human cytomegalovirus antagonizes activation of Fcγ receptors by distinct and synergizing modes of IgG manipulation |
| title_short | Human cytomegalovirus antagonizes activation of Fcγ receptors by distinct and synergizing modes of IgG manipulation |
| title_sort | human cytomegalovirus antagonizes activation of fcγ receptors by distinct and synergizing modes of igg manipulation |
| topic | cytomegalovirus immunoglobulin fc receptors natural killer cells immune evasion |
| url | https://elifesciences.org/articles/63877 |
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