Prion protein alters viral control and enhances pathology after perinatal cytomegalovirus infection
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.
Authors
- Giuseppe Legname (ORCID: https://orcid.org/0000-0003-0716-4393)
- Paola Kučan Brlić (ORCID: https://orcid.org/0000-0002-9178-9128)
- Sébastien Mella (ORCID: https://orcid.org/0000-0002-8679-5718)
- Mijo Golemac (ORCID: https://orcid.org/0000-0002-4486-1887)
- Hermann C. Altmeppen (ORCID: https://orcid.org/0000-0001-9439-6533)
- Vanda Juranić Lisnić (ORCID: https://orcid.org/0000-0002-7182-8927)
- Milena Hasan (ORCID: https://orcid.org/0000-0002-0879-7099)
- Valentina Libri (ORCID: https://orcid.org/0000-0002-2080-1089)
- Stipan Jonjić (ORCID: https://orcid.org/0000-0001-5003-3108)
- Jelena Tomac (ORCID: https://orcid.org/0000-0002-7672-9311)
- Dubravka Karner (ORCID: https://orcid.org/0000-0001-8122-6113)
- Esma Karkeni (ORCID: https://orcid.org/0000-0002-2450-9376)
- Ilija Brizić (ORCID: https://orcid.org/0000-0001-8839-7839)
- T. Rovis
- Astrid Krmpotić (ORCID: https://orcid.org/0000-0001-5470-5370)
- Daria Kveštak (ORCID: https://orcid.org/0000-0001-5280-827X)
- Berislav Lisnić (ORCID: https://orcid.org/0000-0002-3977-6004)
- Maja Cokarić Brdovčak (ORCID: https://orcid.org/0000-0002-9335-8700)
Institutions
- Scuola Internazionale Superiore di Studi Avanzati (IT)
- University of Rijeka (HR)
- Institut Pasteur (FR)
- Universität Hamburg (DE)
- Université Paris Cité (FR)
- University Medical Center Hamburg-Eppendorf (DE)
Publication Details
- Journal
- Nature Communications
- Published
- 2024-09-05
- DOI
- https://doi.org/10.1038/s41467-024-51931-4
- Citations
- 5
- Primary Topic
- Cytomegalovirus and herpesvirus research
- Type
- article
- Field-Weighted Citation Impact
- 1.93
Funders
- Hrvatska Zaklada za Znanost
- European Regional Development Fund