| Autor: |
Dubravka Karner, Daria Kvestak, Paola Kucan Brlic, Maja Cokaric Brdovcak, Berislav Lisnic, Ilija Brizic, Vanda Juranic Lisnic, Mijo Golemac, Jelena Tomac, Astrid Krmpotic, Esma Karkeni, Valentina Libri, Sebastien Mella, Giuseppe Legname, Hermann C. Altmeppen, Milena Hasan, Stipan Jonjic, Tihana Lenac Rovis |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
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| Zdroj: |
Nature Communications, Vol 15, Iss 1, Pp 1-17 (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2041-1723 |
| DOI: |
10.1038/s41467-024-51931-4 |
| Popis: |
Abstract Cytomegalovirus (CMV) infection poses risks to newborns, necessitating effective therapies. Given that the damage includes both viral infection of brain cells and immune system-related damage, here we investigate the involvement of cellular prion protein (PrP), which plays vital roles in neuroprotection and immune regulation. Using a murine model, we show the role of PrP in tempering neonatal T cell immunity during CMV infection. PrP-null mice exhibit enhanced viral control through elevated virus-specific CD8 T cell responses, leading to reduced viral titers and pathology. We further unravel the molecular mechanisms by showing CMV-induced upregulation followed by release of PrP via the metalloproteinase ADAM10, impairing CD8 T cell response specifically in neonates. Additionally, we confirm PrP downregulation in human CMV (HCMV)-infected fibroblasts, underscoring the broader relevance of our observations beyond the murine model. Furthermore, our study highlights how PrP, under the stress of viral pathogenesis, reveals its impact on neonatal immune modulation. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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