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Prion protein alters viral control and enhances pathology after perinatal cytomegalovirus infection

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Prion protein alters viral control and enhances pathology after perinatal cytomegalovirus infection. / Karner, Dubravka; Kvestak, Daria; Kucan Brlic, Paola; Cokaric Brdovcak, Maja; Lisnic, Berislav; Brizic, Ilija; Juranic Lisnic, Vanda; Golemac, Mijo; Tomac, Jelena; Krmpotic, Astrid; Karkeni, Esma; Libri, Valentina; Mella, Sebastien; Legname, Giuseppe; Altmeppen, Hermann C; Hasan, Milena; Jonjic, Stipan; Lenac Rovis, Tihana.

in: NAT COMMUN, Jahrgang 15, Nr. 1, 05.09.2024, S. 7754.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Karner, D, Kvestak, D, Kucan Brlic, P, Cokaric Brdovcak, M, Lisnic, B, Brizic, I, Juranic Lisnic, V, Golemac, M, Tomac, J, Krmpotic, A, Karkeni, E, Libri, V, Mella, S, Legname, G, Altmeppen, HC, Hasan, M, Jonjic, S & Lenac Rovis, T 2024, 'Prion protein alters viral control and enhances pathology after perinatal cytomegalovirus infection', NAT COMMUN, Jg. 15, Nr. 1, S. 7754. https://doi.org/10.1038/s41467-024-51931-4

APA

Karner, D., Kvestak, D., Kucan Brlic, P., Cokaric Brdovcak, M., Lisnic, B., Brizic, I., Juranic Lisnic, V., Golemac, M., Tomac, J., Krmpotic, A., Karkeni, E., Libri, V., Mella, S., Legname, G., Altmeppen, H. C., Hasan, M., Jonjic, S., & Lenac Rovis, T. (2024). Prion protein alters viral control and enhances pathology after perinatal cytomegalovirus infection. NAT COMMUN, 15(1), 7754. https://doi.org/10.1038/s41467-024-51931-4

Vancouver

Karner D, Kvestak D, Kucan Brlic P, Cokaric Brdovcak M, Lisnic B, Brizic I et al. Prion protein alters viral control and enhances pathology after perinatal cytomegalovirus infection. NAT COMMUN. 2024 Sep 5;15(1):7754. https://doi.org/10.1038/s41467-024-51931-4

Bibtex

@article{e3b1305105e04ce495b8bdab19cb913c,
title = "Prion protein alters viral control and enhances pathology after perinatal cytomegalovirus infection",
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.",
keywords = "Animals, Cytomegalovirus Infections/immunology, Cytomegalovirus/immunology, Humans, Mice, CD8-Positive T-Lymphocytes/immunology, Animals, Newborn, Mice, Knockout, Female, Fibroblasts/metabolism, Prion Proteins/metabolism, Mice, Inbred C57BL, Disease Models, Animal, ADAM10 Protein/metabolism",
author = "Dubravka Karner and Daria Kvestak and {Kucan Brlic}, Paola and {Cokaric Brdovcak}, Maja and Berislav Lisnic and Ilija Brizic and {Juranic Lisnic}, Vanda and Mijo Golemac and Jelena Tomac and Astrid Krmpotic and Esma Karkeni and Valentina Libri and Sebastien Mella and Giuseppe Legname and Altmeppen, {Hermann C} and Milena Hasan and Stipan Jonjic and {Lenac Rovis}, Tihana",
note = "{\textcopyright} 2024. The Author(s).",
year = "2024",
month = sep,
day = "5",
doi = "10.1038/s41467-024-51931-4",
language = "English",
volume = "15",
pages = "7754",
journal = "NAT COMMUN",
issn = "2041-1723",
publisher = "NATURE PUBLISHING GROUP",
number = "1",

}

RIS

TY - JOUR

T1 - Prion protein alters viral control and enhances pathology after perinatal cytomegalovirus infection

AU - Karner, Dubravka

AU - Kvestak, Daria

AU - Kucan Brlic, Paola

AU - Cokaric Brdovcak, Maja

AU - Lisnic, Berislav

AU - Brizic, Ilija

AU - Juranic Lisnic, Vanda

AU - Golemac, Mijo

AU - Tomac, Jelena

AU - Krmpotic, Astrid

AU - Karkeni, Esma

AU - Libri, Valentina

AU - Mella, Sebastien

AU - Legname, Giuseppe

AU - Altmeppen, Hermann C

AU - Hasan, Milena

AU - Jonjic, Stipan

AU - Lenac Rovis, Tihana

N1 - © 2024. The Author(s).

PY - 2024/9/5

Y1 - 2024/9/5

N2 - 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.

AB - 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.

KW - Animals

KW - Cytomegalovirus Infections/immunology

KW - Cytomegalovirus/immunology

KW - Humans

KW - Mice

KW - CD8-Positive T-Lymphocytes/immunology

KW - Animals, Newborn

KW - Mice, Knockout

KW - Female

KW - Fibroblasts/metabolism

KW - Prion Proteins/metabolism

KW - Mice, Inbred C57BL

KW - Disease Models, Animal

KW - ADAM10 Protein/metabolism

U2 - 10.1038/s41467-024-51931-4

DO - 10.1038/s41467-024-51931-4

M3 - SCORING: Journal article

C2 - 39237588

VL - 15

SP - 7754

JO - NAT COMMUN

JF - NAT COMMUN

SN - 2041-1723

IS - 1

ER -