UTJECAJ PATOGENOGA PUUMALA I APATOGENOGA TULA ORTOHANTAVIRUSA NA UROĐENI IMUNOSNI ODGOVOR PRIMARNIH MONOCITA I MAKROFAGA

doctoral thesis

• Title (english): THE INFLUENCE OF PATHOGENIC PUUMALA AND APATHOGENIC TULA ORTHOHANTAVIRUS ON THE INNATE IMMUNE RESPONSE OF PRIMARY MONOCYTES AND MACROPHAGES
• Author: Petra Svoboda
• Mentor: Lidija Cvetko Krajinović (mentor)
• Committee member: Snježana Židovec-Lepej (predsjednik povjerenstva)
• Committee member: Andreja Ambriović Ristov (član povjerenstva)
• Committee member: Maja Matulić (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2023, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology
• Universal decimal classification (UDC): 578/579 - Virology. Microbiology

Abstract

Virusi Puumala (PUUV) i Tula (TULV) su RNA virusi koji pripadaju rodu Orthohantavirus
(HTV) porodice Hantaviridae. Virus PUUV patogeni je virus koji uzrokuje hemoragijsku
vrućicu s bubrežnim sindromom, dok se virus TULV smatra apatogenim virusom. Cilj ovog
istraživanja bio je dugotrajnom infekcijom ispitati elemente urođenog imunosnog odgovora
primarnih monocita/makrofaga inficiranih patogenim ili apatogenim ortohantavirusom u
uvjetima in vitro. Rezultati ovog istraživanja pokazali su značajne razlike u obrascu ekspresije
gena koji kodiraju sintezu proupalnih citokina i kemokina, kao i razlike u koncentracijama
pojedinih modulatora biološkog odgovora u ranoj (1 – 24 h od infekcije) i kasnoj (48 h – 7
dana) fazi infekcije. Analiza ekspresije staničnih diferencijacijskih molekula na
monocitima/makrofagima tijekom kultivacije pokazala je smanjenje ekspresije molekula
CD14 i HLA-DR uz značajno povećanu ekspresiju molekule CD206. U ovom radu prvi su
puta dokazane značajne razlike u urođenom imunosnom odgovoru na apatogeni virus TULV
u usporedbi s patogenim virusom PUUV. Rezultati ovog rada ukazuju na kompleksnost
molekularnih mehanizama urođene imunosne reakcije posredovane monocitima/makrofagima
u infekciji patogenim i apatogenim ortohantavirusima.

Abstract (english)

Puumala (PUUV) and Tula (TULV) are RNA viruses, belonging to the genus
Orthohantavirus (HTV), family Hantaviridae. Puumala virus is a pathogenic virus that causes
hemorrhagic fever with renal syndrome, while TULV is considered to be an apathogenic
virus. The aim of this long-term in vitro study was to examine the elements of the innate
immune response of primary monocytes/macrophages infected with pathogenic or
apathogenic orthohantavirus. The results of this research showed significant differences in the
expression pattern of genes encoding the synthesis of pro-inflammatory cytokines and
chemokines, as well as differences in the concentrations of certain biological response
modulators in the early (1-24 h from infection) and late (48 h-7 days) phase of infection.
Analysis of the expression of cell differentiation molecules on monocytes/macrophages
during cultivation showed a decrease in the expression of CD14 and HLA-DR molecules with
a significantly increased expression of the CD206 molecule. We demonstrated here, for the
first time, significant differences in the innate immune response to the apathogenic TULV
compared to the pathogenic PUUV. The results of this work indicate the complexity of the
molecular mechanisms of the innate immune reaction mediated by monocytes/macrophages in
infection with pathogenic and apathogenic orthohantaviruses.

• Keywords: ortohantavirusi; virus Puumala; virus Tula; monociti; makrofagi; imunosni odgovor; urođena imunost; ekspresija gena; ekspresija površinskih molekula; citokini; kemokini; hemoragijska vrućica s bubrežnim sindromom
• Keywords (english): ortohantaviruses; Puumala virus; Tula virus; monocytes; macrophages; immune response; innate immunity; gene expression; surface molecules expression; cytokines; chemokines; hemorrhagic fever with renal syndrome
• Language: croatian
• URN:NBN: urn:nbn:hr:217:231756
• Promotion: 2023
• 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: Embargoed access; Embargo expiration date: 2024-12-20
• Created on: 2023-01-09 12:20:46