prikaz prve stranice dokumenta Uloga NKG2D receptora u imunološkom nadzoru citomegalovirusne infekcije
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doctoral thesis
Uloga NKG2D receptora u imunološkom nadzoru citomegalovirusne infekcije
doktorski rad
2012. urn:nbn:hr:188:386186
Slavuljica, Irena
University of Rijeka
Faculty of Medicine
Department of Infectious Diseases

Cite this document

Slavuljica, I. (2012). Uloga NKG2D receptora u imunološkom nadzoru citomegalovirusne infekcije : doktorski rad (Doctoral thesis). Rijeka: University of Rijeka, Faculty of Medicine. Retrieved from https://urn.nsk.hr/urn:nbn:hr:188:386186

Slavuljica, Irena. "Uloga NKG2D receptora u imunološkom nadzoru citomegalovirusne infekcije : doktorski rad." Doctoral thesis, University of Rijeka, Faculty of Medicine, 2012. https://urn.nsk.hr/urn:nbn:hr:188:386186

Slavuljica, Irena. "Uloga NKG2D receptora u imunološkom nadzoru citomegalovirusne infekcije : doktorski rad." Doctoral thesis, University of Rijeka, Faculty of Medicine, 2012. https://urn.nsk.hr/urn:nbn:hr:188:386186

Slavuljica, I. (2012). 'Uloga NKG2D receptora u imunološkom nadzoru citomegalovirusne infekcije : doktorski rad', Doctoral thesis, University of Rijeka, Faculty of Medicine, accessed 25 December 2024, https://urn.nsk.hr/urn:nbn:hr:188:386186

Slavuljica I. Uloga NKG2D receptora u imunološkom nadzoru citomegalovirusne infekcije : doktorski rad [Doctoral thesis]. Rijeka: University of Rijeka, Faculty of Medicine; 2012 [cited 2024 December 25] Available at: https://urn.nsk.hr/urn:nbn:hr:188:386186

I. Slavuljica, "Uloga NKG2D receptora u imunološkom nadzoru citomegalovirusne infekcije : doktorski rad", Doctoral thesis, University of Rijeka, Faculty of Medicine, Rijeka, 2012. Available at: https://urn.nsk.hr/urn:nbn:hr:188:386186

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Metadata
TitleUloga NKG2D receptora u imunološkom nadzoru citomegalovirusne infekcije : doktorski rad
Title (english)The Role of Receptor NKG2D in the Immune Control of the Cytomegalovirus Infection
AuthorIrena Slavuljica
MentorAstrid Krmpotić (mentor)
MentorStipan Jonjić (komentor)
Committee memberAstrid Krmpotić (član povjerenstva)
Committee memberStipan Jonjić (član povjerenstva)
GranterUniversity of Rijeka
Faculty of Medicine
(Department of Infectious Diseases)
Rijeka
Defense date and country2012-01-01, Croatia
Scientific / art field,
discipline and subdiscipline		BIOMEDICINE AND HEALTHCARE
Clinical Medical Sciences
Infectology
Universal decimal classification
(UDC)		616 - Pathology. Clinical medicine
Abstract
Cilj istraživanja:Razjasniti ulogu receptora NKG2D u uspostavi i održavanjulatentnecitomegalovirusne (CMV) infekcije,tepoticanjuvirus-specifičnogimunološkog odgovora.Materijali i metode: Miševi suinficirani rekombinantnim sojevima MCMV-a kojima su uklonjeni pojedini imunosubverzivni geni za NKG2D ligande (Δm138 MCMV, Δm145MCMV i Δm152MCMV), rekombinantnim MCMV-om koji izražava NKG2D ligand RAE-1γ(RAE-1γMCMV) ili divljim tipom virusa (WT MCMV). Rast virusa u tkivima je uspoređen testom virusnih čistina, a količina virusnog genoma u krvi itkivima kvantitativnim PCR-om. Kinetika i fenotip virus-specifičnih stanica testirani su protočnom citometrijom. Rezultati: Usprkosrane atenuacije, rekombinantni sojevi MCMV-a kojima su uklonjeni pojedini imunosubverzivni geni za NKG2D ligande pokazuju kasni oporavak rasta u žlijezdama slinovnicama. Količina latentnog virusnog genoma u krvi i tkivima, te kinetika i fenotip virus-specifičnog staničnog i humoralnog imunološkog odgovora nakon infekcije delecijskim mutantama MCMV-a i WT MCMV-om su usporedivi. MCMVkoji izražava NKG2D ligand RAE-1γdrastično je atenuiran in vivoine kolonizira žlijezde slinovnice. Smanjen rastRAE-1γMCMV-a rezultira bržim nestajanjem virusne DNK iz krvi i smanjenom količinom latentnog virusnog genoma u tkivima odraslih, imunokompetentnih miševa i novookoćenih miševa s nedozrelim imunološkim sustavom. Infekcija ovim virusomje uspješno kontrolirana i u imunokompromitiranog domaćina kao što su miševa kojima nedostaje receptor za tip I interferone i u miševa imunokompromitiranih γ-zračenjem. Stanični i humoralni imunološki odgovor potaknut infekcijom RAE-1γMCMV-om usporediv je s onim nakon infekcije WT MCMV-om i štiti domaćina od letalne CMV infekcije. RAE-1γMCMV uspostavlja latencijus mogućnošćureaktivacije virusa u uvjetima imunosupresije. Usprkos snažnog selekcijskog tlaka imunološkog sustavaRAE-1γizražen kao transgen u RAE-1γMCMV genomu ne podliježe mutacijama.Imunizacija mišica RAE-1γMCMV-om štiti njihovumladunčadod CMV bolesti posredovano transplacentarno prenesenim virus-specifičnim protutijelima. IIZaključak: Receptor NKG2D igra važnu ulogu u uspostavi i održavanjulatentne CMV infekcije, te poticanju virus-specifičnog imunološkog odgovora. RekombinantanCMV konstruiran tako da izražava NKG2D ligand RAE-1γ je izvrstan kandidatza sigurnu i učinkovitu CMV vakcinuili vektor za izražaj antigena drugih patogena.
Abstract (english)
Objectives:Of the study are to clarify the role of receptor NKG2D during latent cytomegalovirus (CMV) infection and in the process of priming and maintenance of virus-specific immune response. Materials and methods:Mice were infected with recombinant MCMVs lacking one of the NKG2D imunoevasion genes (Δm138 MCMV, Δm145MCMV and Δm152MCMV), MCMV expressingNKG2D ligand RAE-1γ(RAE-1γMCMV) or wild type MCMV (WT MCMV). Viral titers were determined by virus titration and viral DNA load by quantitative PCR. Kinetics and phenotype of virus-specific lymphocytes were tested by FACS analysis. Results: Despite early attenuation, recombinant MCMVs lacking any of the NKG2D immunovasion genes show late recoveryof infectious virus in salivary glands. Latent virus DNA load as well as kinetics and phenotype of virus-specific immune response after infection withMCMV deletion mutants and WT MCMV are comparable. RAE-1γMCMV is strongly attenuated in vivoand failsto establish persistentinfection in salivary glands. Strong attenuation of RAE-1γMCMV results in faster clearance of virus DNA from blood and significantly lower latent virus DNA load in tissues in adult, immunocompetent mice and in the newborn mice with immature immune system. Despite tight innate immune control RAE-1γMCMV infection elicits strong and enduring antiviral immune response that confersprotection against lethal MCMV infection. Strong attenuation does not prevent RAE-1γMCMV from establishing latency and reactivating upon immunosuppression. Infection with RAE-1γMCMV presentsa low risk for disease even in severely immunodeficient host such as mice lacking receptor for type I interferons and mice immunocompromised by γ-irradiation. In spite of the strong selective pressure by the immune system RAE-1γ remains intact during latent RAE-1γMCMV infection. Maternal RAE-1γMCMV immunization protects neonatal mice from MCMV infection upon placental transfer of antiviral antibodies. IVConclusions: Receptor NKG2D plays a major role during latent CMV infection and in the process of priming and maintenanceof virus-specific immune response. Recombinant CMV designedto expressNKG2D ligand is anexcellent candidate for a safe and immunogenicCMV vaccine or CMV-based vaccine vector.
Keywords
Keywords (english)
Languagecroatian
URN:NBNurn:nbn:hr:188:386186
Promotion2012
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)
Catalog URLhttps://libraries.uniri.hr/cgi-bin/ucat/unilib.cgi?form=D1121204073
Type of resourceText
Extent135 str; 30 cm
File originBorn digital
Access conditionsClosed access
Terms of useLicence In copyright icon
Created on2017-01-19 17:43:51