Naslov
Immunological role of cellular prion protein (PrPC) during cytomegaloviral infection

Autori
Karner, Dubravka ; Kveštak, Daria ; Kučan Brlić, Paola ; Cokarić Brdovčak, Maja ; Lisnić, Berislav ; Brizić, Ilija ; Juranić Lisnić, Vanda ; Golemac, Mijo ; Tomac, Jelena ; Legname, Giuseppe ; Altmeppen, Hermann C ; Hasan, Milena ; Jonjić, Stipan ; Lenac Roviš, Tihana

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Prion 2022 Conference abstracts: pushing the boundaries / - : Prion ; Informa UK Limited, Taylor & Francis Group, 2022, 170-171

Skup
Prion 2022

Mjesto i datum
Göttingen, Njemačka, 13.09.2022. - 16.09.2022

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
congenital viral infection ; neuroinflammation ; cytomegalovirus ; host-pathogen interaction ; prion protein physiology ; immune system control ; ADAM10

Sažetak
Aims: Human cytomegalovirus (HCMV) infection is the most common congenital viral infection and the leading cause of lasting perinatal brain damage, with the inflammatory response being the primary cause of pathogenic manifestations. Accordingly, it has been shown that anti-inflammatory drugs can reduce abnormalities in newborn mice infected with mouse cytomegalovirus (MCMV). Since contemporary anti-viral drugs have inadequate efficiency, finding new therapeutic targets that can reduce brain damage is of utmost importance. There are growing indications that cellular prion protein (PrPC) dampens the immune response in various organs and prevents collateral, immune response- mediated pathologies. In addition to being expressed on immune cells, PrPC can also bind to immune cells, suggesting its interaction with immune receptors. Our primary goal is to characterize the role and impact of PrPC on the course and severity of congenital cytomegalovirus infection and associated brain pathology. Material and Methods: Intraperitoneal infection of newborn mice with MCMV recapitulates the major hallmarks of human congenital CMV infection: virus dissemination to the brain parenchyma, neuroinflammation and altered brain development. To determine the correlation between PrPC expression, inflammation and developmental and functional changes, we com-pare the following parameters in infected newborn WT and PrPC-KO mice: i) viral load ; ii) cytokines (FACS, xMAP technology) ; iii) activation status and transcriptional profiles of immune cells (FACS, scRNA-seq) ; iv) CMV-related brain anomalies (IHC). In addition, we monitor the impact of CMV on PrPC biology at the cellular level in vitro (antibody development, FACS, confocal microscopy, immunoblot). Results: We show that CMV infection in different cell lines and primary cells affects the amount of PrPC. After initial strong induction of PrPC expression at early time points of infection, cell-associated PrPC levels are largely reduced, partially by triggering its ADAM10-mediated cell surface shedding. Intriguingly, PrPC-KO mice have significantly lower virus titers in multiple organs, including the brain. Immune cell subsets and mechanisms responsible for more efficient virus clearance in the absence of PrPC protein are still being investigated. Conclusions: Obtained data indicate that PrPC is involved in the immune response to CMV infection in newborn mice. Absence of PrPC improves control of the virus due to enhanced immune system activation.

Izvorni jezik
Engleski

Znanstvena područja
Biologija, Temeljne medicinske znanosti

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