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Multimodal HLA-I genotype regulation by human cytomegalovirus US10 and resulting surface patterning

التفاصيل البيبلوغرافية
العنوان: Multimodal HLA-I genotype regulation by human cytomegalovirus US10 and resulting surface patterning
المؤلفون: 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
المصدر: eLife, Vol 13 (2024)
بيانات النشر: eLife Sciences Publications Ltd, 2024.
سنة النشر: 2024
المجموعة: LCC:Medicine
LCC:Science
LCC:Biology (General)
مصطلحات موضوعية: human cytomegalovirus, MHC class I, US10, peptide loading complex, immunoevasin, tapasin, Medicine, Science, Biology (General), QH301-705.5
الوصف: 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.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 2050-084X
Relation: https://elifesciences.org/articles/85560; https://doaj.org/toc/2050-084X
DOI: 10.7554/eLife.85560
URL الوصول: https://doaj.org/article/c867fd290b5f4af9870c2dc3f63a87b4
رقم الأكسشن: edsdoj.867fd290b5f4af9870c2dc3f63a87b4
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:2050084X
DOI:10.7554/eLife.85560