Uloga proteina ADAR1 u replikaciji herpes simpleks virusa 1

Đukić, Nina

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master's thesis

Uloga proteina ADAR1 u replikaciji herpes simpleks virusa 1

Rijeka: University of Rijeka, 2020. urn:nbn:hr:193:755962

Đukić, Nina

University of Rijeka
Department of Biotechnology

Cite this document

APA 6th Edition

Đukić, N. (2020). Uloga proteina ADAR1 u replikaciji herpes simpleks virusa 1 (Master's thesis). Rijeka: University of Rijeka. Retrieved from https://urn.nsk.hr/urn:nbn:hr:193:755962

MLA 8th Edition

Đukić, Nina. "Uloga proteina ADAR1 u replikaciji herpes simpleks virusa 1." Master's thesis, University of Rijeka, 2020. https://urn.nsk.hr/urn:nbn:hr:193:755962

Chicago 17th Edition

Đukić, Nina. "Uloga proteina ADAR1 u replikaciji herpes simpleks virusa 1." Master's thesis, University of Rijeka, 2020. https://urn.nsk.hr/urn:nbn:hr:193:755962

Harvard

Đukić, N. (2020). 'Uloga proteina ADAR1 u replikaciji herpes simpleks virusa 1', Master's thesis, University of Rijeka, accessed 05 October 2023, https://urn.nsk.hr/urn:nbn:hr:193:755962

Vancouver

Đukić N. Uloga proteina ADAR1 u replikaciji herpes simpleks virusa 1 [Master's thesis]. Rijeka: University of Rijeka; 2020 [cited 2023 October 05] Available at: https://urn.nsk.hr/urn:nbn:hr:193:755962

IEEE

N. Đukić, "Uloga proteina ADAR1 u replikaciji herpes simpleks virusa 1", Master's thesis, University of Rijeka, Rijeka, 2020. Available at: https://urn.nsk.hr/urn:nbn:hr:193:755962

Cite this item: https://urn.nsk.hr/urn:nbn:hr:193:755962

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Metadata

Title	Uloga proteina ADAR1 u replikaciji herpes simpleks virusa 1
Title (english)	Roles of ADAR1 protein in herpes simplex virus 1 replication
Author	Nina Đukić
Mentor	Igor Jurak (mentor)
Committee member	Jelena Ban (predsjednik povjerenstva)
Committee member	Ivana Ratkaj (član povjerenstva)
Granter	University of Rijeka (Department of Biotechnology) Rijeka
Defense date and country	2020-07-17, Croatia
Scientific / art field, discipline and subdiscipline	BIOTECHNICAL SCIENCES Biotechnology Biology
Abstract	Infekcija virusom herpes simpleksa 1 (HSV-1) uzrokuje nekoliko bolesti, u rasponu od kožnih, oralnih i genitalnih infekcija do fatalnog encefalitisa (1). Unatoč napretku protuvirusnih terapija koje su značajno smanjile morbiditet i mortalitet HSV-a kod imunokompromitiranih osoba, i dalje je od velikog interesa pobliže razumijevanje elemenata koji pridonose virulenciji HSV-1. Iz tog razloga postoji velika potreba za detaljnom analizom, različitih faktora domaćina koje virus koristi za promicanje infekcije kao i faktora obrane koji djeluju protivno HSV-1 infekciji (2). Jedan od potencijalnih faktora koji utječe na HSV-1 virulenciju je adenozin deaminaza koja djeluje na RNA (ADAR1). Njegova funkcija A-u-I uređivanja dvolančanih RNA nedavno je prepoznata kao ključan proces u označavanju dsRNA kao vlastite, prevenirajući tako aktivaciju urođenog imunološkog odgovora te djelujući na razvoj i ishod imunološki posredovanih bolesti i infekcija. Prethodna istraživanja pokazala su da, ovisno o specifičnim interakcijama virusa i domaćina, ADAR1 može djelovati protuvirusno, ali i provirusno. Do danas, njegova uloga u HSV-1 infekciji nije istražena, stoga je cilj ovog rada bio odrediti utjecaj ADAR1 enzima na replikaciju HSV-1. U svrhu ostvarenja tog cilja korištene se stanice s utišanom ekspresijom ADAR1 te stanice negativne kontrole, kod kojih je praćena razina faktora urođenog imunološkog odgovora i virusnih proteina. Dobiveni rezultati ukazuju na protuvirusni učinak ADAR1 tijekom rane faze HSV-1 infekcije s obzirom da se njegovim utišavanjem značajno povećala razina neposredno ranih virusnih proteina te faktora uređenog imunološkog odgovora eIf-2α, čija aktivnost potiče ekspresiju virusnih gena. S druge strane, utišavanje ekspresije ADAR1 nije dovelo do značajne promjene u replikaciji virusa između ispitivanih stanica, stoga je pretpostavljeno da njegova protuvirusna aktivnost nema dovoljno snažan učinak koji bi uzrokovao veći poremećaj u replikaciji HSV-1. Zaključno, rezultati ovog rada potvrđuju ulogu ADAR1 tijekom HSV-1 infekcije te ukazuju na ADAR1 kao potencijalnu metu za pojačavanje protuvirusnog imunološkog odgovora.
Abstract (english)	Herpes simplex virus type-1 (HSV-1) infection can cause several diseases, ranging from cutaneous, oral and genital infections to fatal encephalitis (1). Despite advances in antiviral therapies that have significantly reduced HSV morbidity and mortality, a closer understanding of the elements contributing to HSV-1 virulence remains of great interest. For this reason, there is a great need for a detailed analysis of the host factors that the virus uses to promote infection as well as defense factors that act against HSV-1 infection (2). One of the potential factors affecting HSV-1 virulence is ADAR1. A-to-I editing by ADAR1 has recently been recognized as a key process in marking dsRNA as self, thus preventing activation of the innate immune response and affecting the development and outcome of immune-mediated diseases and infections. Previous research has shown that depending on different virus-host combinations, ADAR1 can have both antiviral and proviral effects. To date, its role in HSV-1 infection has not been evaluated, therefore the aim of this study was to investigate the role of ADAR1 in HSV-1 infection. To achieve this goal, cells with downregulated ADAR1 expression and negative control cells were used to examine the level of innate immune factors and viral proteins. The obtained results indicate the antiviral effect of ADAR1 during the early phase of HSV-1 infection since its downregulation significantly increased the level of immediate-early viral proteins and translation initiation factor eIf-2α, which promotes the expression of viral genes. On the other hand, we did not observe a difference in virus replication when ADAR1 was downregulated, therefore this data suggests that its antiviral activity is not strong enough to cause HSV-1 replication defect. In summary, the results of this study confirm the role of ADAR1 during HSV-1 infection and pointing towards ADAR1 as a potential target to boost antiviral immune response.
Keywords
Keywords (english)
Language	croatian
URN:NBN	urn:nbn:hr:193:755962
Study programme	Title: Biotechnology in medicine Study programme type: university Study level: graduate Academic / professional title: magistar/magistra biotehnologije u medicini (magistar/magistra biotehnologije u medicini)
Type of resource	Text
File origin	Born digital
Access conditions	Access restricted to students and staff of home institution
Terms of use
Repository	Repository of the University of Rijeka, Department of Biotechnology
Created on	2020-07-16 20:20:47