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Effect of ADAR1 enzyme on hepatitis C virus life cycle
Kubů, Martin ; Vopálenský, Václav (advisor) ; Fraiberk, Martin (referee)
Hepatitis C virus (HCV) is a virus of the family Flaviviridae whose genome consists of ,,+RNA" molecule. It causes the disease hepatitis Cepatitida typu C, which affects tens of millions of people worldwide. Although there is an effective treatment for this type of hepatitis, a preventive vaccine against the HCV virus has not yet been developed. Several ambigious works focused on the relationship between HCV and the enzyme adenosine deaminase acting on double-stranded RNA 1 (ADAR1) were published in the past. This dimeric double-stranded RNA binding enzyme is a part of innate immunity and causes catalytic conversion of adenosine to inosine, which is recognized by cellular mechanisms as guanine, which ultimately leads to mutations in the affected dsRNA molecule. The works published so far attribute an antiviral function to the ADAR1 enzyme in the context of HCV infection. However, vectors containing the entire HCV genome were not used in these works, and a cell line with deletion od the ADAR1 gene has never been used so far. The actual relationship between the ADAR1 enzyme and the HCV virus has not yet been reliably verified. The aim of this thesis was to gain a deeper understanding of the relationship between the HCV virus and the ADAR1 enzyme. For this task, HCV permissive Huh7.5 cell lines with...
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Studies of properties of viral capsid proteins and development of recombinant vaccines and diagnostic components based on artificial viral structures
Fraiberk, Martin ; Forstová, Jitka (advisor) ; Hubálek Kalbáčová, Marie (referee) ; Hejnar, Jiří (referee)
The aim of this study was to develop a system for easy production of different veterinary chimeric vaccines based on stable mouse polyomavirus (MPyV) structures. The system is designed for antigens that are problematic in production or stability. First, universal vectors for baculovirus-directed production of chimeric MPyV VLPs or pentamers based on the major capsid protein VP1 were designed to be exploited as vaccines against other pathogens. The different strategies used in this study are based on: A) exposure of selected immunogenic epitopes on the surface of MPyV VLPs by inserting them into a surface loop of the VP1 protein, B) insertion of foreign protein molecules inside the VLPs, or C) fusion of a foreign protein or its part with the C-terminus of VP1 protein, thus forming giant pentamers of a chimeric protein. Candidate vaccine antigens against porcine circovirus 2 (PCV2), the causative agent of porcine circovirus 2 systemic diseases (PCV2-SD) which causes significant economic losses in swine breeding, were prepared using the constructed vectors. All candidate vaccines induced the production of antibodies against the capsid protein of PCV2 after immunization of mice. The candidate vaccine Var C based on fusion of MPyV and PCV2 capsid proteins, is able to induce production of antibodies with...
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Formation of anti-hCMV immunity
Písková, Lucie ; Žůrková, Kamila (advisor) ; Fraiberk, Martin (referee)
The human cytomegalovirus (HCMV) is an ancient double-stranded DNA virus that belongs to subfamily β Herpesvirinae and is ubiquitous in human population. Like other herpesviruses infections, the HCMV primary infection leads to a lifelong latency and the virus reactivates from latency periodically through the whole life. The transmission of this virus depends on direct contact among people. The primary HCMV infection is usually asymptomatic in immunocompetent individuals but the reactivated virus is a major cause of diseases in immunocompromised individuals including AIDS patients and allo-graft transplant recipients. This work represents a report about HCMV and its coexistence with the host immune system. The thesis also contains information about complications caused by HCMV in patients who underwent solid-organ or hematopoietic stem cell transplantation.
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Antiviral vaccination - hepatitis A virus
Rančáková, Hana ; Drda Morávková, Alena (advisor) ; Fraiberk, Martin (referee)
Hepatitis A is an ifectious disease caused by Hepatitis A virus (HAV) from Picornaviridae family. HAV is an uneveloped virus composed of positive single-stranded RNA and a capsid with icosahedral symmetry. This infection is wide-spread and endemic in many regions of the world. The main way of transmission is throught the fecal-oral route. The possible symptoms, that can appear during the disease are fever, fatigue, muscle-pain, nausea, vomiting and afterward yellowish discoloration of the skin and mucous membranes. On the other hand, the disease can proceed without any symptoms, that is common especially in the childhood. The people can shelter from the disease by aplication of vaccine. At this time there are four inactivated hepatitis A vaccines at the world market. All of the vaccines are highly effective and provide a long-term protection. This work is intent on the infection of hepatitis A virus, the possibilities of prevention with vaccines and the inclusion of curriculum about viral diseases and vaccination in the School Educational Programmes.
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The role of HOXA9 gene in leukemogenesis
Rejlová, Kateřina ; Starková, Júlia (advisor) ; Fraiberk, Martin (referee)
The evolutionarily conserved family of homeobox genes plays an important role in the development of the anterior-posterior body axis of vertebrates. These genes significantly affect hematopoiesis, the development of blood cells. Extensive studies on homeobox genes in normal hematopoiesis confirmed their role also in leukemogenesis. Since the neoplastic transformation of blood cells, i.e. leukemia, is the most frequent malignancy in children, it has become a major subject of research for many scientists. Precisely in what stage of the malignant transformation the homeobox genes take part has not been shown yet. Neither is it known whether HOX genes are crucial in pathogenesis or whether their deregulation is only a side effect of leukemogenesis. The most studied homeobox gene in leukemogenesis is the HOXA9 gene, which showed correlation with the prognosis of patients with certain leukemias. Many studies describe the effect of HOXA9 in leukemic cell transformation, suggesting this gene could be a promising future target in leukemia therapy. This work is focused on the HOXA9 gene and its association with leukemic transformation of blood cells.
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Awareness of contagious disease in mind of pupils at basic and secondary schools.
Peštová, Ilona ; Rajsiglová, Ina (advisor) ; Fraiberk, Martin (referee)
Infectious diseases are a very hot topic nowadays in society. In recent years, there were several epidemics, infectious diseases (hepatitis A, Avian influenza, pandemic influenza A) and nobody knows when will the next "new" infection. At the outbreak of epidemics, there is great interest in the company to obtain information about the disease, but often also to unnecessary panic, because the media often publish incorrect information. It would be preferable, in order to improve public awareness and prevent the unnecessary spread of disease. Great emphasis should be given to prevent the disease - primarily on immunization, hygiene rules and principles of safe sex. Quality information should be mainly from teachers in teaching their pupils, as is clear from research books, infectious diseases are only mentioned in textbooks and the number of substantive information in them is missing. The fact that pupils of primary schools and grammar schools with basic information on infectious diseases do not meet in the classroom, evidenced by the results of a survey carried out in the 6th classes and first year at selected elementary schools and grammar schools in Prague. To raise awareness of the pupils in school was to create a methodical manual for teachers, which summarizes information about bacterial and...
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Chimeric antigen receptors (CARs) in cancer treatment
Fejtková, Martina ; Macková, Jana (advisor) ; Fraiberk, Martin (referee)
Chimeric antigen receptor (CAR) is an artificial T-lymphocyte receptor consisting of extracellular single chain antibody serving as antigen binding site, transmembrane part and intracellular part which activates the cell. Therefore, it has the advantage of targeted specificity of monoclonal antibody and artificially strengthened activation of the T-lymphocyte by activation and costimulation domains. T-lymphocyte with CAR is able to locate and eliminate target cell with given surface antigen and also activate other compartments of the immune system by cytokine production. CAR T-lymphocytes have a huge potential for treatment of hematomalignancies and research also comes with new achievements in CAR modification for elimination of solid tumors.
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Yeast retrograde signaling pathway between mitochondria and the nucleus
Podholová, Kristýna ; Palková, Zdena (advisor) ; Fraiberk, Martin (referee)
Retrograde signaling pathway is the pathway between mitochondria and nucleus. This pathway helps Saccharomyces cerevisiae to cope with worsening of conditions of life, such as depletion of rich nutrient sources and necessity of use poor resources, reduction of mitochondrial membrane potential, or loss of mitochondrial DNA causing disturbances in the citric acid cycle. Most of these conditions are associated with aging yeast populations. Key retrograde pathway proteins include RTG transcription factors Rtg1p/Rtg3p and cytoplasmic protein Rtg2p. Retrograde pathway is upregulated by several positive and negative regulators including the TOR pathway, which negatively regulates retrograde pathway. The retrograde pathway target genes include genes coding for tricarboxylic cycle enzymes, peroxisomal enzymes, transporters and other enzymes of anaplerotic pathways. Retrograde response help cells to modify their metabolism so that they are able to overcome unfavorable environmental conditions in which they live. Powered by TCPDF (www.tcpdf.org)
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