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, Vol. 15, No. 1, 05.09.2024, p. 7754.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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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 -