|
|
POSITIVE AND NEGATIVE HOST FACTORS OF AVIAN SARCOMA AND LEUKOSIS VIRUSES
Krchlíková, Veronika ; Elleder, Daniel (advisor) ; Růžek, Daniel (referee) ; Španielová, Hana (referee)
Identification and characterization of the host cell factors that either support or inhibit virus replication constitutes a major direction in virological research. In this work we focus on several such host factors in the context of avian cell. Chicken Tva, cell entry receptor for subgroups A and K of Avian sarcoma and leukosis virus (ASLV), was identified to be orthologous to human receptor for cellular uptake of cobalamin (Cbl). Here, we describe Cbl uptake in chicken cells and its dependency on Tva. Additionally, we characterize in vivo Tva knockout in chicken. Chicken Tvb receptor conferring susceptibility to subgroups B, D and E of ASLV was previously shown to participate in virus-induced cytopathic effects. In this work, we identify a natural ligand of Tvb and investigate its participation in apoptosis. RIG-I-like receptors (RLR) are a key family of cytosolic viral RNA sensors. The activation of these receptors leads to establishment of an antiviral state in the cell. In this study, we describe repeated evolutionary losses of RLR genes in birds: the loss of MDA5 in two avian orders and the loss of RIG-I in multiple species. Tetherin is an antiviral restriction factor blocking the release of newly formed viral particles. We identify tetherin orthologs in avian species and investigate...
|
|
|
Inflammation and cancer in germ-free vs. conventionally reared animals
Čaja, Fabián ; Vannucci, Luca Ernesto (advisor) ; Tlaskalová - Hogenová, Helena (referee) ; Smrž, Daniel (referee)
Inflammation is considered as one of the main defence mechanisms of the immune system against threats that occur in the body. When present in its acute form, minimal or no detectable subsequent damage of original affected tissue exists. The more pathological form, chronic inflammation, is associated with permanent damage of the tissue and typically a hallmark of various diseases such as ulcerative colitis or colon carcinogenesis. These two pathologies are evolving in the unique colon microenvironment, where intensive interaction between the host cells and bacteria is present. The aim of our study was to investigate the immunological (ELISA, FACS, RT-PCR) and structural (histology, confocal microscopy) changes in the colon mucosa of Wistar-AVN rats induced by dextran sodium sulphate (DSS) to produce colon colitis and by azoxymethane (AOM) to produce colon carcinogenesis. Conventional (CV) and also germ-free (GF) reared animals were used to investigate the effects of the mucosal inflammation activated by the administered inducers as well as the role of colon microbiota - as promoters of a continuous immune activation - in the modulation of immunity and collagen scaffold remodelling. Our results showed that even in the early period after the induction, both inducers produced a smouldering...
|
|
|
The role of PML nuclear bodies in herpesvirus infection
Bártová, Jana ; Šroller, Vojtěch (advisor) ; Saláková, Martina (referee)
PML nuclear bodies are protein structures in the cell nucleus that regulate many important cellular processes and are also implicated in antiviral defense. The permanent components of these nuclear bodies include PML, Sp100 and Daxx proteins, many other proteins are transiently associated with PML bodies. PML body components can be SUMOylated, this posttranslational modification is important for the formation of PML bodies and regulation of their function. Components of PML bodies such as PML, Sp100 and Daxx can act as restriction factors limiting the replication of many DNA and RNA viruses. Defense mechanisms mediated by PML bodies are suppressed by viral proteins that inactivate individual components or disrupt the structure of PML bodies. This thesis focuses on the role of PML bodies as restriction factors during infection by DNA viruses of the Herpesviridae family and describes the interactions of PML bodies and viral proteins, using herpes simplex virus 1, human cytomegalovirus and Epstein-Barr virus as examples. Keywords: PML nuclear bodies, restriction factor, antiviral defense, innate immunity, herpesviruses
|
|
|
Sensing of MPyV infection by innate immunity sensors
Rjabčenko, Boris ; Forstová, Jitka (advisor) ; Anděra, Ladislav (referee) ; Mělková, Zora (referee)
Host sensors that recognize pathogen associated molecular patterns and the mechanisms of innate immune response to mouse polyomavirus (MPyV) infection were the main topics of current work. We found that MPyV did not induce interferon (IFN) production during early events of infection, but induced interleukin-6 (IL-6) and other cytokine production without inhibiting virus multiplication. Cytokine microenvironment changed the phenotype of adjacent non infected fibroblasts toward the cancer-associated fibroblast (CAF)-like phenotype. We identified Toll-like receptor 4, a sensor of the innate immunity system, to be responsible for infection dependent IL-6 production. In an effort to determine whether and where virions are released from endosomal compartments into the cytosol, we found that the hydrophobic domains of minor capsid proteins, exposed on the surface of virions after their partial disassembly in the ER, play an important role in effective escape of virions from the lumen part of endoplasmic reticulum into the cytosol, Although naked, partially disassembled virions appear before translocation to the nucleus in the cytosol, viral DNA is not recognized by cytosolic sensors at this phase of infection Sensing of MPyV resulting in IFN production occurs first during viral replication. Mutant virus,...
|
|
| |
|
|
Biomarkers in children with periodic fever syndromes
Król, Petra ; Doležalová, Pavla (advisor) ; Šedivá, Anna (referee) ; Krbková, Lenka (referee)
- 4 - Abstract Introduction: Periodic fever syndromes are clinical entities classified as autoinflammatory diseases. The most of the periodic fever syndromes have genetic predisposition (monogenic periodic fever syndromes). PFAPA (Periodic Fever, Aphtous stomatitis, Pharyngitis a Adenitis) syndrome is an idiopathic disease with unknown aetiology. Results: In our study, we described the largest clinical series of patients with PFAPA syndrome from a single center. The laboratory results have confirmed uncomplicated course of PFAPA syndrome. In our measurements we observed significantly higher levels of serum cytokines (IL-1β and IFN-γ) during episodes of fever in PFAPA patients compared to the control group. Our measurements showed increased numbers of plasma cells in the peripheral blood of PFAPA patients. We have found increased levels of naïve CD4 and CD8 T cells and approximately 2-fold higher proportion of CD8 T cells in tonsils of PFAPA patients. Significant differences were also present at levels of IFN-γ, IL-1β, IL-6 and TNF-α in stimulated supernatants compared to supernatants from unstimulated peripheral blood from patients with PFAPA syndrome. Measurements of bacterial profile showed individual microbial profile in patients. Conclusion: Removal of the tonsillar tissue with the potential...
|
|
|
Induction of innate immune response against intracellular bacterium Francisella tularensis
Sommerová, Gabriela ; Konečná, Klára (advisor) ; Myslivcová Fučíková, Alena (referee)
Background: The purpose of this bachelor thesis is to describe Francisella tularensis and activation of innate immunity during host infection. Main findings: The main findings of the work include the method of recognition of F. tularensis via Toll-like receptors, the production of cytokines and chemokines and the subsequent involvement of other components of innate immunity, including neutrophils, NK cells, or humoral components of the immune response, which also includes complement. The information is based on a number of studies performed mainly on mouse models. Conclusions: The intracelullar bacterium F. tularensis is known to cause tularemia. Its high infectivity, together with the high risk of death in the lung form, raises great concerns about the misuse of this bacterium as a biological weapon. To date, not all of its mechanisms of pathogenesis are known, which is a major problem in the development of effective vaccines. The induction of innate immunity appears to be very important in the host's defense against F. tularensis. However, despite several decades of research, the mechanisms of F. tularensis involved in host cell manipulation, including the regulation of the induction of immune response to F. tularensis infection, have still not been fully elucidated. Key words: Francisella...
|
|
|
Trans-species polymorphism in selected innate immunity genes in tits (Paridae family)
Těšický, Martin ; Vinkler, Michal (advisor) ; Štefka, Jan (referee)
Adaptation of host receptor system to optimal detection of infection-related structures is one of the key evolutionary challenges of immunity in host-pathogen interactions. Toll-like receptors (TLRs) are genetically variable molecules of vertebrate innate immunity that recognise danger signals, e.g. pathogenic molecules. Examination of genetic variation in TLRs may reveal mechanisms of host immunity adaptation to pathogenic pressure at molecular level. Trans-species polymorphism (TSP) is a phenomenon which assumes that several identical alleles or allelic lineages are inherited from ascendant to descendant species and these may be subsequently maintained over a long period of time in a polymorphic state. Whereas in adaptive immune genes the concept of TSP is well understood, little is presently known about TSP in innate immune genes such as TLRs. In this thesis I describe genetic polymorphism in functionally-relevant regions of TLR4 and TLR5 in 192 individuals representing 20 species Paridae family (tits, chickadees and titmice). These two receptors bind mainly bacterial ligands (TLR4 detects lipopolysaccharide and TLR5 detects flagellin), being among the first ones to trigger immune response to bacterial pathogens. To differentiate presumed TSP from gene flow among species, intron sequences of six...
|
|
| |
|
|
Molecular interactions of Staphylococcus aureus with the host
Cabrnochová, Marie ; Melter, Oto (advisor) ; Vopálenský, Václav (referee)
The aim of this thesis is to summarize S. aureus interactions with selected mechanisms of innate host immunity especially interactions with neutrophils and processes on the cell level which lead to host colonization. S. aureus surface proteins MSCRAMM interact with host cell surface proteins such as fibrinogen, keratin and thereby mediate adhesion to the host cell, which is an essential point for colonization of the host cell. The central mechanism of innate immunity against any S. aureus infection is the interaction of the pathogen with neutrophils, which produce neutrophil extracellular traps and phagocytes S. aureus cells. A crucial role in the elimination of bacterial cells in the phagosome of neutrophils is lysis by the antimicrobial peptides and degradation of bacterial biomolecules by the oxygen radicals. S. aureus defence mechanisms against action of immune system are considered to be virulence factors, due to its contribution to the establishment of the infection. These mechanisms are based on cell wall modification, inhibition of neutrophil chemotaxis, and production of enzymes that inhibit the effect of antimicrobial peptides, lysozyme, oxygen and nitrogen radicals. Expression of virulence factors of a particular S. aureus strain and host-specific risk factors can lead through successful...
|
guest ::
