Human cytomegalovirus antagonizes activation of Fcγ receptors by distinct and synergizing modes of IgG manipulation
© 2021, Kolb et al..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:10 |
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| Enthalten in: |
eLife - 10(2021) vom: 16. März |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Kolb, Philipp [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 25.08.2021 Date Revised 25.08.2021 published: Electronic Citation Status MEDLINE |
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| doi: |
10.7554/eLife.63877 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM322808685 |
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| 245 | 1 | 0 | |a Human cytomegalovirus antagonizes activation of Fcγ receptors by distinct and synergizing modes of IgG manipulation |
| 264 | 1 | |c 2021 | |
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| 500 | |a Date Completed 25.08.2021 | ||
| 500 | |a Date Revised 25.08.2021 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2021, Kolb et al. | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a cytomegalovirus | |
| 650 | 4 | |a fc receptors | |
| 650 | 4 | |a immune evasion | |
| 650 | 4 | |a immunoglobulin | |
| 650 | 4 | |a immunology | |
| 650 | 4 | |a infectious disease | |
| 650 | 4 | |a inflammation | |
| 650 | 4 | |a microbiology | |
| 650 | 4 | |a natural killer cells | |
| 650 | 4 | |a virus | |
| 650 | 7 | |a Carrier Proteins |2 NLM | |
| 650 | 7 | |a Glycoproteins |2 NLM | |
| 650 | 7 | |a Immunoglobulin G |2 NLM | |
| 650 | 7 | |a Membrane Glycoproteins |2 NLM | |
| 650 | 7 | |a Receptors, IgG |2 NLM | |
| 650 | 7 | |a UL119-UL118 glycoprotein, Human cytomegalovirus |2 NLM | |
| 650 | 7 | |a Viral Proteins |2 NLM | |
| 650 | 7 | |a gp34 protein, cytomegalovirus |2 NLM | |
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| 700 | 1 | |a Sievert, Annika |e verfasserin |4 aut | |
| 700 | 1 | |a Reinhard, Henrike |e verfasserin |4 aut | |
| 700 | 1 | |a Merce-Maldonado, Eva |e verfasserin |4 aut | |
| 700 | 1 | |a Le-Trilling, Vu Thuy Khanh |e verfasserin |4 aut | |
| 700 | 1 | |a Halenius, Anne |e verfasserin |4 aut | |
| 700 | 1 | |a Gütle, Dominique |e verfasserin |4 aut | |
| 700 | 1 | |a Hengel, Hartmut |e verfasserin |4 aut | |
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