Multimodal HLA-I genotype regulation by human cytomegalovirus US10 and resulting surface patterning
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 g...
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| Hauptverfasser: | , , , , , , , , , , , , , , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
20 June, 2024
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| In: |
eLife
Year: 2024, Jahrgang: 13, Pages: 1-29 |
| ISSN: | 2050-084X |
| DOI: | 10.7554/eLife.85560 |
| Online-Zugang: | Verlag, kostenfrei, Volltext: https://doi.org/10.7554/eLife.85560
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| Verfasserangaben: | 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 |
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| 245 | 1 | 0 | |a Multimodal HLA-I genotype regulation by human cytomegalovirus US10 and resulting surface patterning |c 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 |
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| 520 | |a 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. | ||
| 650 | 4 | |a Antigen Presentation | |
| 650 | 4 | |a Cytomegalovirus | |
| 650 | 4 | |a Gene Expression Regulation | |
| 650 | 4 | |a Genotype | |
| 650 | 4 | |a Histocompatibility Antigens Class I | |
| 650 | 4 | |a Host-Pathogen Interactions | |
| 650 | 4 | |a human | |
| 650 | 4 | |a human cytomegalovirus | |
| 650 | 4 | |a Humans | |
| 650 | 4 | |a immunoevasin | |
| 650 | 4 | |a infectious disease | |
| 650 | 4 | |a MHC class I | |
| 650 | 4 | |a microbiology | |
| 650 | 4 | |a peptide loading complex | |
| 650 | 4 | |a Protein Binding | |
| 650 | 4 | |a tapasin | |
| 650 | 4 | |a US10 | |
| 650 | 4 | |a Viral Proteins | |
| 650 | 4 | |a viruses | |
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