The immunoregulatory role of PrPC in antiviral immune response following cytomegaloviral infection
Project title: The immunoregulatory role of PrPC in antiviral immune response following cytomegaloviral infection
Grantor: Croatian Science Foundation
Grantor’s website: www.hrzz.hr
Coordinator: Prof. Dr. Tihana Lenac Rovis
Research team:
Dr. Milena Hasan
Dr. Paola Kucan Brlic
Dr. Maja Cokaric Brdovcak
Dr. Hrvoje Simic
Dubravka Karner, mag. biotech. in med.
Total funding: EUR 201.401,41
Dubravka Karner osvojila nagradu za najbolju usmenu prezentaciju na Godišnjem skupu HID-a 2024.
Nekada doktorandica, a danas poslijedoktorandica, Dubravka Karner sudjelovala je kao članica društva na Godišnjem skupu Hrvatskog imunološkog društva (HID), održanom u listopadu 2024. godine u Sisku.
Dubravka je na skupu sudjelovala s usmenim izlaganjem na temu “Cellular prion protein alters viral control and enhances pathology after perinatal cytomegalovirus infection”, u kojem je predstavila rezultate istraživanja provedenog u sklopu projekta. Za ovo izlaganje dobila je nagradu za najbolju usmenu prezentaciju – Bright Sparks Award, koju dodjeljuje društvo.
Godišnji sastanak HID-a redovito okuplja stručnjake i znanstvenike, pretežno iz Europe. Na skupu 2024. godine izlagali su sljedeći pozvani predavači:
- Prof. Bence Rethi, Odjel za medicinu, Karolinska Institutet, Stockholm, Švedska
- Prof. Maria Pia Felli, Odjel za eksperimentalnu medicinu, Sveučilište Sapienza u Rimu, Italija
- Prof. Berislav Bošnjak, Institut za imunologiju, Medicinski fakultet u Hannoveru, Njemačka
- Prof. Sanja Novak, Centar za regenerativnu medicinu i razvoj skeleta, Stomatološki fakultet, UConn Health, Farmington, Connecticut, SAD
- Prof. Igor Aurer, Zavod za hematologiju, Klinički bolnički centar Zagreb, Hrvatska
- Prof. Tomislav Kelava, Zavod za fiziologiju i imunologiju, Medicinski fakultet, Zagreb, Hrvatska
- Dr. Marko Šestan, Zavod za histologiju i embriologiju, Medicinski fakultet, Sveučilište u Rijeci, Hrvatska
- Dr. Ilija Brizić, Centar za proteomiku, Medicinski fakultet, Sveučilište u Rijeci, Hrvatska
HID je aktivni član Europske federacije imunoloških društava (EFIS). EFIS je neprofitna krovna organizacija koja okuplja 35 europskih imunoloških društava, uključujući i udruženja iz Euroazije i Bliskog istoka. Svaki aktivni član bilo kojeg društva povezanog s EFIS-om automatski se smatra članom EFIS-a i kao takav može koristiti sve pogodnosti EFIS-ovih programa. Danas EFIS povezuje gotovo 14.000 istraživača i kliničara koji djeluju u području imunologije i alergologije.
Protekla radionica, održana 24. i 25. travnja 2023., okupila je stručnjake iz područja single-cell analize i slikovnih tehnika. Tijekom ova dva dana, sudionici su imali priliku čuti zanilljiva predavanja i sudjelovati u praktičnim radionicama.
Naglasak prvog dana bio je na inovativnim strategijama za mjerenje fenotipa i profila stanica s pojedinačnom razlučivošću, te na mogućnostima suradnje s francuskim istraživačima, uključujući Pasteur Institut i platformu za "spatial transcripomics".
Drugi dan fokusirao se na primjeni oslikavanja u svijetlom polju i fluorescenci te na praktičnom radu s histološkim skenerom.
Zahvaljujemo svim sudionicima na sudjelovanju. Nadamo se da će stečeno znanje doprinijeti daljnjem napretku u istraživanjima pojedinačnih stanica i slikovnim tehnikama.
Tim Medicinskog fakulteta u Rijeci, uz podršku Instituta Pasteur, uspješno je identificirao ključne CD8 T limfocite nakon citomegalovirusne infekcije. Nakon pripreme uzoraka u Rijeci, RNA sekvenciranje na razini jedne stanice izvedeno je na Institutu Pasteur.
Brief description:
Primary HCMV infection in adults is generally asymptomatic because of the effective immune response of the host. However, HCMV is a recognized cause of morbidity and mortality in immunodeficient individuals. The most prominent medical problem remains congenital HCMV infection, since it carries a risk of permanent brain damage in children and no uniquely established or effective treatment methods are available.
Because HCMV is strictly species-specific, animal models, most commonly the mouse model (MCMV), are used to study the course and consequences of infection. It is particularly important for this project to emphasize that our group has developed a model for congenital MCMV infection in infected new-born mice to investigate brain damage and hearing loss. Our research has shown that MCMV-related brain pathology is mainly due to a strong inflammatory immune response. Accordingly, the use of anti-inflammatory drugs has led to reduced brain damage and inflammatory-induced defects in infected new-born mice.
In the case of the PrPC protein, we consider it an ideal candidate for a new target molecule that could reduce brain damage, for several reasons. PrPC has been proven to be a significant factor in both key processes leading to permanent brain damage due to congenital HCMV infection: a) PrPC is predominantly expressed in brain tissue where it has a neuroprotective role through regulation of oxidative stress and cell death; and b) PrPC is a stress-inducible molecule and immune cell modulator. We have gained extensive experience and developed sophisticated assays in the field of molecular immunosuppressive virus mechanisms and immune cell modulation when investigating PVR protein as a part of previous, completed HRZZ Project coordinated by T. Lenac Rovis. Here, too, our primary goal is to understand the underlying molecular mechanisms and immune principles by which the PrPC protein participates in the course and consequences of congenital HCMV infection. The ability to use the advanced instruments available in the laboratories of the Institut Pasteur and the knowledge and techniques to be adopted there will mark a major leap forward. Should the project's results confirm our hypotheses based on strong preliminary results, we will take advantage of the fact that years of PrPC protein transformation studies have produced a number of preparations that may affect its functioning. These include small molecules, peptides and anti-PrPC antibodies, and the fact that any treatment preparation had to be delivered to brain tissue. The principal investigator (T. Lenac Rovis) has gained experience in this field during her postdoctoral training at the Prion Biology laboratory at SISSA in Italy.
In conclusion - the way in which the PrPC protein modulates a) cell death and b) the immune response in the brain is unknown. We consider our model of congenital CMV infection to be appropriate for understanding the true physiological role of this protein, which has remained unclear to this day. We believe that by characterizing the mechanisms of reducing neurological damage resulting from CMV infection, through modulation of the PrPC protein, it could also become a new target molecule for anti-oxidative or anti-inflammatory drugs.
