UTJECAJ NUKLEOZIDNIH ANALOGA NA GENSKU VARIJABILNOST I INFEKTIVNOST VIRUSA ZAUŠNJAKA

doctoral thesis

• Title (english): INFLUENCE OF NUCLEOSIDE ANALOGUES ON THE HETEROGENEITY AND INFECTIVITY OF MUMPS VIRUS
• Author: Mirna Jurković
• Mentor: Maja Jagušić (mentor)
• Committee member: Snježana Židovec-Lepej (predsjednik povjerenstva)
• Committee member: Dubravko Forčić (član povjerenstva)
• Committee member: Silvija Černi (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2024, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology
• Universal decimal classification (UDC): 577 - Biochemistry. Molecular biology. Biophysics

Abstract

Pojava epidemija uzrokovanih virusom zaušnjaka čak i u procijepljenim populacijama ukazuje na potrebu razvoja učinkovitijih cjepiva i specifične antivirusne terapije. U ovom istraživanju ispitan je potencijal triju nukleozidnih analoga (ribavirina, 5-fluorouracila, 5-azacitidina) za moduliranje genske varijabilnosti ovog virusa u smjeru njegove atenuacije ili ekstinkcije metodama virusne kvantifikacije te analize genoma na temelju rezultata sekvenciranja nove generacije. Pokazano je da sva tri nukleozidna analoga u genom uvode specifične promjene, mijenjaju stopu mutacije i smanjuju titar virusa u staničnoj kulturi. Virusi tretirani 5-azacitidinom razvili su rezistentnost na nukleozidni analog. Tretman virusa koncentracijom ribavirina od 500 μM doveo je do ekstinkcije virusa. Rezultati ovog istraživanja pridonose boljem razumijevanju biologije i evolucije virusa zaušnjaka, naglašavajući potencijal mutageneze kao jednog od mehanizama djelovanja sva tri nukleozidna analoga na ovaj virus.

Abstract (english)

Intermittent mumps virus outbreaks within vaccinated populations underscore the imperative for advancing more efficacious vaccines and specific antiviral therapy. This study investigates the potential of three nucleoside analogs (ribavirin, 5-fluorouracil, 5-azacytidine) for modulating the genetic variability of this virus towards its attenuation or extinction using virus quantification methods and next-generation sequencing genome analysis. Results show that these analogs induce specific genomic changes, alter mutation rates, and reduce virus titre in cell culture. Notably, viruses treated with 5-azacytidine exhibit resistance to the nucleoside analog. Additionally, a 500 μM ribavirin concentration leads to virus extinction. The research enhances understanding of mumps virus biology and evolution, emphasizing mutagenesis as a key mechanism for all three nucleoside analogs.

• Keywords: virus zaušnjaka; varijabilnost virusne populacije; nukleozidni analozi; mutageneza
• Keywords (english): mumps virus; virus population diversity; nucleoside analogues; mutagenesis
• Language: croatian
• URN:NBN: urn:nbn:hr:217:181057
• Promotion: 2024
• Project: Number: KK.01.1.1.01.0006; Title: Jačanje kapaciteta CERVIRVAC-a za istraživanja u virusnoj imunologiji i vakcinologiji; Title: Strengthening the capacity of CerVirVac (Croatian Centre of Excellence for Virus Immunology and Vaccines) for research in viral immunology and vaccinology; Leader: Stipan Jonjić; Jurisdiction: eu; Funder: Europska komisija; Funding stream: European Regional Development Fund
• Study programme: Title: Doctoral study; Study programme type: university; Study level: postgraduate; Academic / professional title: doktor/doktorica znanosti u području prirodnih znanosti (doktor/doktorica znanosti u području prirodnih znanosti)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2024-09-03 10:35:51