Human cytomegalovirus antagonizes activation of Fcγ receptors by distinct and synergizing modes of IgG manipulation

eLife

Annika Sievert¹  Anne Halenius¹  Hartmut Hengel¹  Philipp Kolb¹  Dominique Gütle¹  Katja Hoffmann¹  Vu Thuy Khanh Le-Trilling²  Eva Merce-Maldonado³  Henrike Reinhard³ 

[1] Faculty of Medicine, Albert-Ludwigs-University Freiburg, Freiburg, Germany;Institute of Virology, University Medical Center, Albert-Ludwigs-University Freiburg, Freiburg, Germany;Institute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany;Institute of Virology, University Hospital Düsseldorf, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany;

关键词: cytomegalovirus;    immunoglobulin;    fc receptors;    natural killer cells;    immune evasion;    Virus;   

DOI  :  10.7554/eLife.63877

来源: eLife Sciences Publications, Ltd

【 摘 要 】

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.

【 授权许可】

CC BY