Mutacije u genu za nukleokapsidni protein virusa hepatitisa C u oboljelih od kroničnoga hepatitisa

doctoral thesis

• Title (english): Mutations in core region of hepatitis C virus in patients with chronic hepatitis
• Author: Bojana Mohar Vitezić
• Mentor: Blaženka Grahovac (mentor); MBZ: 112820
• Committee member: Snježana Židovec-Lepej (član povjerenstva); MBZ: 228211
• Committee member: Silvija Černi (član povjerenstva)
• Committee member: Sandra Milić (član povjerenstva); MBZ: 243151
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2016, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology
• Universal decimal classification (UDC): 576 - Cellular and subcellular biology. Cytology

Abstract

Virus hepatitisa C (HCV) je globalno prisutan patogen koji u zaraženih osoba može uzrokovati različite kliničke slike. Genetika HCV-a i infekcija su kompleksni i specifični procesi, zbog međusobnog odnosa domaćina i virusa, te uzrokuju različiti klinički tijek bolesti jetre. Nukleokapsidni protein je kompleksan HCV protein koji može u određenoj mjeri modificirati ulazak HCV virusa u stanicu, replikacijski ciklus te formiranje i oslobađanje HCV-a iz stanice. Nukleokapsidni protein sudjeluje pri vezivanju s mnogim staničnim proteinima i usmjerava određene stanične signalne puteve, te u konačnici može pridonijeti razvoju hepatokarcinogeneze. Cilj rada bio je istražiti postoje li korelacije između mutacija u nukleokapsidnoj regiji, te virusnih i patohistoloških parametara u kroničnoj infekciji HCV-om, u uzorcima seruma i jetre 87 ispitanika, te utvrditi postoji li povezanost prisutnih mutacija s progresivnijim tijekom jetrene bolesti. Rezultati rada pokazuju značajnu pozitivnu korelaciju podtipa 1b i koncentracije virusne RNA u krvi s prisutnošću mutacija R70Q, T75A i M91L/C nukleokapsidnog gena. Patohistološki parametri (stupanj aktivnosti hepatitisa i stadij fibroze) udruženi su s prisutnošću mutacija R70Q i M91L/C. Rezultati istraživanja pokazuju da učestalost mutacija i određeni tip mutacija pozitivno koreliraju s progresivnijim i težim tijekom jetrene bolesti.

Abstract (english)

Hepatitis C virus (HCV) is a globally prevalent pathogen with diverse clinical outcomes. Considering the interlinking relation of the host and the virus, the genetics of HCV and infection in humans is specific and individual . Thus, it can result in a variety of different disease course among the infected hepatitis C patients. HCV core is complex protein, capable of modifying hepatitis C life cycle by participating in interactions with host proteins, altering cellular signaling pathways and contributing in hepatocarcinogenesis. The aim of this study was to investigate correlations between the changes of core region and the viral and patohistological parameters of chronic hepatitis C in liver and serum samples of 87 patients. The aim was also to determine coherence of core region mutations and liver disease progression. Results of this study indicate significant correlation of genotype 1b and basal viremia with presence of R70Q, T75A i M91L/C mutations. Patohistological parameters (hepatitis activity grade and fibrosis stage) were associated with presence of R70Q and M91L/C mutations. Finally, results of our study indicate that frequency and the type of mutations positively correlates with liver disease progressivity.

• Keywords: hepatitis C; nukleokapsidni protein; analiza slijeda nukleotida; kronični hepatitis C; virusni i patohistološki parametri
• Keywords (english): hepatitis C; core protein; sequencing; chronic hepatitis C; viral and patohistological parameters
• Language: croatian
• URN:NBN: urn:nbn:hr:217:192434
• Study programme: Title: Biology; Study programme type: university; Study level: postgraduate; Academic / professional title: doktor/doktorica znanosti, područje prirodnih znanosti, polje biologija (doktor/doktorica znanosti, područje prirodnih znanosti, polje biologija)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Access restricted to students and staff of home institution
• Created on: 2017-05-16 09:43:09