| Online-Ressource |
Verfasst von: | Gerke, Carolin [VerfasserIn]  |
| Bauersfeld, Liane [VerfasserIn]  |
| Schirmeister, Ivo [VerfasserIn]  |
| Mireisz, Chiara Noemi-Marie [VerfasserIn]  |
| Oberhardt, Valerie [VerfasserIn]  |
| Mery, Lea [VerfasserIn]  |
| Wu, Di [VerfasserIn]  |
| Jürges, Christopher Sebastian [VerfasserIn]  |
| Spaapen, Robbert M. [VerfasserIn]  |
| Mussolino, Claudio [VerfasserIn]  |
| Le, Vu Thuy Khanh [VerfasserIn]  |
| Trilling, Mirko [VerfasserIn]  |
| Dölken, Lars [VerfasserIn]  |
| Paster, Wolfgang [VerfasserIn]  |
| Erhard, Florian [VerfasserIn]  |
| Hofmann, Maike [VerfasserIn]  |
| Schlosser, Andreas [VerfasserIn]  |
| Hengel, Hartmut [VerfasserIn]  |
| Momburg, Frank [VerfasserIn]  |
| Halenius, Anne [VerfasserIn]  |
Titel: | Multimodal HLA-I genotype regulation by human cytomegalovirus US10 and resulting surface patterning |
Verf.angabe: | Carolin Gerke, Liane Bauersfeld, Ivo Schirmeister, Chiara Noemi-Marie Mireisz, Valerie Oberhardt, Lea Mery, Di Wu, Christopher Sebastian Jürges, Robbert M. Spaapen, Claudio Mussolino, Vu Thuy Khanh Le-Trilling, Mirko Trilling, Lars Dölken, Wolfgang Paster, Florian Erhard, Maike Hofmann, Andreas Schlosser, Hartmut Hengel, Frank Momburg, Anne Halenius |
E-Jahr: | 2024 |
Jahr: | 20 June, 2024 |
Umfang: | 29 S. |
Illustrationen: | Illustrationen |
Fussnoten: | Gesehen am 20.02.2025 |
Titel Quelle: | Enthalten in: eLife |
Ort Quelle: | Cambridge : eLife Sciences Publications, 2012 |
Jahr Quelle: | 2024 |
Band/Heft Quelle: | 13(2024) vom: Juni, Artikel-ID e85560, Seite 1-29 |
ISSN Quelle: | 2050-084X |
Abstract: | Human leucocyte antigen class I (HLA-I) molecules play a central role for both NK and T-cell responses that prevent serious human cytomegalovirus (HCMV) disease. To create opportunities for viral spread, several HCMV-encoded immunoevasins employ diverse strategies to target HLA-I. Among these, the glycoprotein US10 is so far insufficiently studied. While it was reported that US10 interferes with HLA-G expression, its ability to manipulate classical HLA-I antigen presentation remains unknown. In this study, we demonstrate that US10 recognizes and binds to all HLA-I (HLA-A, -B, -C, -E, -G) heavy chains. Additionally, impaired recruitment of HLA-I to the peptide loading complex was observed. Notably, the associated effects varied significantly dependending on HLA-I genotype and allotype: (i) HLA-A molecules evaded downregulation by US10, (ii) tapasin-dependent HLA-B molecules showed impaired maturation and cell surface expression, and (iii) β2m-assembled HLA-C, in particular HLA-C*05:01 and -C*12:03, and HLA-G were strongly retained in complex with US10 in the endoplasmic reticulum. These genotype-specific effects on HLA-I were confirmed through unbiased HLA-I ligandome analyses. Furthermore, in HCMV-infected fibroblasts inhibition of overlapping US10 and US11 transcription had little effect on HLA-A, but induced HLA-B antigen presentation. Thus, the US10-mediated impact on HLA-I results in multiple geno- and allotypic effects in a so far unparalleled and multimodal manner. |
DOI: | doi:10.7554/eLife.85560 |
URL: | Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.
kostenfrei: Volltext: https://doi.org/10.7554/eLife.85560 |
| DOI: https://doi.org/10.7554/eLife.85560 |
Datenträger: | Online-Ressource |
Sprache: | eng |
Sach-SW: | Antigen Presentation |
| Cytomegalovirus |
| Gene Expression Regulation |
| Genotype |
| Histocompatibility Antigens Class I |
| Host-Pathogen Interactions |
| human |
| human cytomegalovirus |
| Humans |
| immunoevasin |
| infectious disease |
| MHC class I |
| microbiology |
| peptide loading complex |
| Protein Binding |
| tapasin |
| US10 |
| Viral Proteins |
| viruses |
K10plus-PPN: | 1917688431 |
Verknüpfungen: | → Zeitschrift |
Multimodal HLA-I genotype regulation by human cytomegalovirus US10 and resulting surface patterning / Gerke, Carolin [VerfasserIn]; 20 June, 2024 (Online-Ressource)