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doctoral thesis
ULOGA CITOMEGALOVIRUSNOG PROTEINA MCK-2 U TROPIZMU VIRUSA I IMUNOLOŠKOM ODGOVORU
Rijeka: University of Rijeka, Faculty of Medicine, 2016. urn:nbn:hr:184:867954
Brizić, Ilija
University of Rijeka
Faculty of Medicine
Center for Proteomics

Institutional repository: Repository of the University of Rijeka, Faculty of Medicine

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Brizić, I. (2016). ULOGA CITOMEGALOVIRUSNOG PROTEINA MCK-2 U TROPIZMU VIRUSA I IMUNOLOŠKOM ODGOVORU (Doctoral thesis). Rijeka: University of Rijeka, Faculty of Medicine. Retrieved from https://urn.nsk.hr/urn:nbn:hr:184:867954

Brizić, Ilija. "ULOGA CITOMEGALOVIRUSNOG PROTEINA MCK-2 U TROPIZMU VIRUSA I IMUNOLOŠKOM ODGOVORU." Doctoral thesis, University of Rijeka, Faculty of Medicine, 2016. https://urn.nsk.hr/urn:nbn:hr:184:867954

Brizić, Ilija. "ULOGA CITOMEGALOVIRUSNOG PROTEINA MCK-2 U TROPIZMU VIRUSA I IMUNOLOŠKOM ODGOVORU." Doctoral thesis, University of Rijeka, Faculty of Medicine, 2016. https://urn.nsk.hr/urn:nbn:hr:184:867954

Brizić, I. (2016). 'ULOGA CITOMEGALOVIRUSNOG PROTEINA MCK-2 U TROPIZMU VIRUSA I IMUNOLOŠKOM ODGOVORU', Doctoral thesis, University of Rijeka, Faculty of Medicine, accessed 09 November 2024, https://urn.nsk.hr/urn:nbn:hr:184:867954

Brizić I. ULOGA CITOMEGALOVIRUSNOG PROTEINA MCK-2 U TROPIZMU VIRUSA I IMUNOLOŠKOM ODGOVORU [Doctoral thesis]. Rijeka: University of Rijeka, Faculty of Medicine; 2016 [cited 2024 November 09] Available at: https://urn.nsk.hr/urn:nbn:hr:184:867954

I. Brizić, "ULOGA CITOMEGALOVIRUSNOG PROTEINA MCK-2 U TROPIZMU VIRUSA I IMUNOLOŠKOM ODGOVORU", Doctoral thesis, University of Rijeka, Faculty of Medicine, Rijeka, 2016. Available at: https://urn.nsk.hr/urn:nbn:hr:184:867954

Metadata
TitleULOGA CITOMEGALOVIRUSNOG PROTEINA MCK-2 U TROPIZMU VIRUSA I IMUNOLOŠKOM ODGOVORU
Title (english)THE ROLE OF CYTOMEGALOVIRUS MCK-2 PROTEIN IN VIRAL TROPISM AND IMMUNE RESPONSEW
AuthorIlija Brizić
MentorStipan Jonjić (mentor)
Committee memberAlemka Markotić (predsjednik povjerenstva)
Committee memberNatalia Kučić (član povjerenstva)
Committee memberKristina Grabušić (član povjerenstva)
Committee memberStipan Jonjić (član povjerenstva)
GranterUniversity of Rijeka
Faculty of Medicine
(Center for Proteomics)
Rijeka
Defense date and country2016-11-08, Croatia
Scientific / art field,
discipline and subdiscipline		BIOMEDICINE AND HEALTHCARE
Basic Medical Sciences
Universal decimal classification
(UDC)		61 - Medical sciences
Abstract
Cilj istraživanja: Glikoproteinski dimeri gH/gL citomegalovirusa čine komplekse s drugim virusnim proteinima koji određuju tropizam virusa. Naša istraživanja ukazivala su da protein MCK-2 mišjeg citomegalovirusa (MCMV) formira kompleks s dimerom gH/gL. S obzirom na važnu ulogu kompleksa gH/gL u ulasku virusa u stanicu glavni cilj ovoga istraživanja je bio definirati ulogu kompleksa gH/gL/MCK-2 u tropizmu virusa, odrediti važnost neutralizirajućih protutijela na ovaj kompleks te utjecaj proteina MCK-2 na imunološki odgovor. Materijali i metode: Stanične linije i laboratorijski miševi su inficirani divljim tipom virusa ili virusnim mutantima kojima je onemogućen izražaj proteina MCK-2, proteina gO, ili oba proteina. Udjeli inficiranih stanica, te fenotipski i funkcionalni status imunoloških stanica tijekom MCMV-infekcije određeni su protočnom citometrijom. Razine virusa u organima inficiranih miševa određene su testom virusnih čistina. Rezultati: Kompleks gH/gL/MCK-2 pospješuje infekciju makrofaga, te doprinosi infekciji i širenju virusa na drugim vrstama stanica, napose kada nema kompleksa gH/gL/gO. Protutijela koja nastaju tijekom infekcije specifična za kompleks gH/gL/MCK-2 imaju sposobnost neutralizacije virusa, međutim, njihov učinak in vivo je ograničen. Izražaj proteina MCK-2 potiče odgovor CD8+ limfocita T, pri čemu kontrola virusa putem stanica NK ima važnu ulogu. Zaključci: Dobiveni rezultati su objasnili ulogu kompleksa gH/gL/MCK-2 u tropizmu virusa. Kompleks gH/gL/MCK-2 bitan je za infekciju makrofaga, ali i za širenje virusa unutar organa što posreduje zajedno s kompleksom gH/gL/gO. Protutijela koja prepoznaju kompleks gH/gL/MCK-2 mogu oslabiti infekciju citomegalovirusom. Osim uloge u tropizmu virusa protein MCK-2 važan je u regulaciji imunološkog odgovora na virus.
Abstract (english)
Objectives: Glycoprotein dimers gH/gL are interacting with other viral proteins and resulting complexes are determining tropism of cytomegalovirus (CMV). Our preliminary results suggested that mouse CMV (MCMV) protein MCK-2 forms a gH/gL complex. Since gH/gL complexes have an important role in virus entry, the goal of this research was to define the role of MCMV gH/gL/MCK-2 complex in viral tropism, to assess the impact of antibodies raised against this complex in virus control and to assess the impact of the protein MCK-2 on immune response. Materials and methods: Cell lines and laboratory mice were infected with wild type virus or viral mutants lacking expression of MCK-2, gO, or both proteins. Frequency of infected cells and functional and phenotypic status of immune cells during MCMV infection were assesed by flow cytometry. Level of virus in organs was determined by plaque assay. Results: The gH/gL/MCK-2 complex enhances infection of macrophages, and contributes to infection of other cell types. Antibodies specific for the gH/gL/MCK-2 complex that develop during the infection have the ability to neutralize virus infection. However, in vivo their antiviral role is limited. MCK-2 expression also enhances the CD8+ T cell response, and this function is NK cell dependent. Conclusion: The results of this study explain the role of gH/gL/MCK-2 complex in virus tropism. This complex is important for infection of macrophages, but also compensates the role of gH/gL/gO complex in virus spread in other cell types. Antibodies recognizing the gH/gL/MCK-2 complex can reduce the virus burden during MCMV infection. MCK-2 protein also contributes to shaping of CD8+ T cell response.
Keywords
Keywords (english)
Languagecroatian
URN:NBNurn:nbn:hr:184:867954
Study programmeTitle: Biomedicine Postgraduate (doctoral) study programme
Study programme type: university
Study level: postgraduate
Academic / professional title: doktor/doktorica znanosti, područje biomedicine i zdravstvo (doktor/doktorica znanosti, područje biomedicine i zdravstvo)
Type of resourceText
File originBorn digital
Access conditionsAccess restricted to students and staff of home institution
Terms of useLicence In copyright icon
Created on2022-03-16 17:02:43