Usporedba aktivacije urođenog imunosnog odgovora u stanicama monocita i mišića čovjeka nakon infekcije adenovirusima tipa 5, 26 i 35

master's thesis

• Title (english): The comparison of the induction of innate immune response in human monocytes and muscle cells after infection with the adenovirus type 5, 26 and 35
• Author: Ivana Radić
• Mentor: Andreja Ambriović Ristov (mentor)
• Granter: University of Zagreb; Faculty of Food Technology and Biotechnology; (Department of Biochemical Engineering); (Laboratory for Biology and Microbial Genetics); Zagreb
• Defense date and country: 2018-07-20, Croatia
• Scientific / art field, discipline and subdiscipline: BIOTECHNICAL SCIENCES; Biotechnology

Abstract

Adenovirus tipa 5 (AdV5) najkorišteniji je viralni vektor u genskoj terapiji pri čemu je jedan od nedostataka njegova velika seroprevalencija u populaciji što smanjuje mogućnost njegove uporabe te imunogenost vektora. Iz tog razloga, priseže se korištenju vektora koji u populaciji imaju nisku seroprevalenciju, kao što su adenovirus tipa 26 (AdV26) i adenovirus tipa 35 (AdV35). Urođeni imunosni odgovor čini prvu liniju obrane organizma od patogena, pa tako i adenovirusa. Infekcija adenovirusima potiče proizvodnju brojnih citokina i kemokina koji djeluju protuupalno te eliminiraju strane antigene. Adenovirusi različitih serotipova izazivaju urođeni imunosni odgovor različitog intenziteta. U ovom radu uspoređena je aktivacija urođenog imunosnog odgovora u stanicama monocita i mišića čovjeka nakon infekcije AdV5, AdV26 i AdV35. Uočeno je da AdV35 u stanicama monocita i mišića čovjeka izaziva najsnažniji urođeni imunosni odgovor i to poticanjem ekspresije gena koji kodiraju za IL-6, IL-8, IL-1β i TNFα odnosno povećanim lučenjem IL-6 i IL-8. Urođeni imunosni odgovor koji AdV26 potiče u RD i THP-1 stanicama sličan je odgovoru koji potiče infekcija s AdV5. Poticanje urođenog imunosnog odgovora infekcijom AdV5, AdV26 i AdV35 posredovano je s pIRF-3 i NF-κB. Ovi rezultati upućuju na potencijal AdV26 i AdV35 kao povoljnih vektora za prijenos gena i vakcinaciju.

Abstract (english)

Adenovirus type 5 (AdV5) is the most widely used viral vector in gene therapy, however its immunogenicity and high seroprevalence in the population reduces the possibility of usage of this vector. For those reasons, vectors with low seroprevalence in the population such as adenovirus type 26 (AdV26) and adenovirus type 35 (AdV35), are used as an alternative approach. The innate immune response is the first line of defense of the organism from pathogens, thus also adenoviruses. Adenoviral infection triggers the production of numerous anti-inflammatory cytokines and chemokines that eliminate foreign antigens. Different serotypes of adenoviruses cause innate immune responses of varying intensity. This thesis compares the induction of innate immune responses in human monocytes and muscle cells after AdV5, AdV26 and AdV35 infection. It was observed that AdV35 in human monocytes and muscle cells induces the most powerful innate immune response by stimulating expression of genes encoding IL-6, IL-8, IL-1β and TNFα, thus increasing IL-6 and IL-8 secretion. The innate immune response triggered by AdV26 in human monocytes and muscle cells is similar to the response triggered by AdV5 infection. The induction of the innate immune response by AdV5, AdV26 and AdV35 infection is mediated by pIRF-3 and NF-κB. These findings point to the potential of AdV26 and AdV35 as favorable vectors for gene transfer and vaccination.

• Keywords: adenovirus; urođeni imunosni odgovor; seroprevalencija; genska terapija
• Keywords (english): adenovirus; innate immune response; seroprevalence; gene therapy
• Language: croatian
• URN:NBN: urn:nbn:hr:159:959265
• Study programme: Title: Molecular Biotechnology; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra inženjer/inženjerka molekularne biotehnologije (magistar/magistra inženjer/inženjerka molekularne biotehnologije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2019-11-28 08:00:56