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The role of JC virus in etiology and therapy of multiple sclerosis.
Musil, Dominik ; Španielová, Hana (advisor) ; Šmahelová, Jana (referee)
JCPyV is a human polyomavirus. Infections caused by this type of virus is often without any clinical symptoms and JCPyV mostly persists in kidneys of human for the rest of the life. The most serious disease caused by the JCPyV is progressive multifocal leukoencephalopathy, which causes severe demyelination of neurons in the brain. Multiple sclerosis, as well as progressive multifocal leukoencephalopathy, is characterised by the demyelinization of neurons. In the past few years, it was shown that the development of PML occurs in some pacients who suffered from multiple sclerosis and who were treated with the monoclonal antibody called natalizumab (Tysabri). This text describes the analysis of the conncetion between viral infection of JCPyV and the etiology of multiple sclerosis and progressive multifocal leukoencephalopathy. As the risk factors for the progression of progressive multifocal leukoencephalopathy in natalizumab treated multiple sclerosis patients the duration of the use, previous immunosuppressant therapy and the presence of the anti-JCPyV antibodies have been demonstrated. In addition to these risk factors, it has also been demonstrated that the people with progressive multifocal leukoencephalopathy have mutations in the genome of virus in the regulatory region, as well as in the...
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Effect of pH on initiation of viral infection
Vomáčka, Petr ; Španielová, Hana (advisor) ; Šmahelová, Jana (referee)
In organisms, acidic pH occurs either in the intracellular or extracellular environment. Intracellularly an acidic pH is found in particular cellular compartments, such as early and late endosomes or lysosomes. In the extracellular space, the acidic pH is found in hypoxic tissues, or in tissues where inflammation or tumour growth occurs. The value of the pH is usually in the range of approximately from 5.5 up to 6.5. This work focuses on the description of the conformation changes of viral proteins, which occur due to a decreased pH and lead to escape of viral components from membrane compartments. Changes in pH in organelles of endocytic pathways as well as changes in extracellular pH affect significantly the infection of many viruses. Research on the role of pH during the viral can bring important information for the development of antiviral and anticancer treatment. Key words: virus, conformation, pH, receptor, endocytosis
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Detection and pathological impact of human Parvovirus B19 in the general population and in the immunocompromissed host
Dubišová, Mária ; Hubáček, Petr (advisor) ; Šmahelová, Jana (referee)
Parvovirus B19 is a non-enveloped single-stranded DNA virus, belonging to the Parvoviridae family. Despite parvoviruses are one of the smallest DNA viruses, some of them are able to infect humans. In general, most of humans experienced parvovirus B19 infection. In case of infection in healthy individual there are usually no complications. Most frequently infected are children and their symptomatic infection is known as fifth disease - erythema infectiosum (EI). However, serious complications may occur if infected person suffers from erythropoiesis disorders, weakened immunity or is pregnant. This thesis aimes the structure of the virus, the course of the infection, infectious diseases caused by parvovirus B19 and particular genotypes especially to pathogenesis of specific disorders. Key words: Parvovirus B19, single-stranded DNA virus, erythroid progenitor cells, Gb4, imunokompromissed host, anemia
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Histone modifications and methylation of polyomaviral genomes during the infection
Mrkáček, Michal ; Forstová, Jitka (advisor) ; Šmahelová, Jana (referee)
Similarly to other viruses, polyomaviruses require for their successful replication enzymes and other proteins encoded by their host cells. Additionally, because of their relatively small genome with only a few genes, polyomaviruses utilize for their efficient replication cellular regulation mechanisms. One of these regulations are posttranslational modifications of histones, which form nucleosomes together with viral DNA. The spectrum of these modifications is very wide, but in case of polyomaviruses, almost only ones studied are histone acetylations and methylations. Second possible regulation is a methylation of cytosine in CpG dinucleotides, which is associated with repression of gene expression. Current knowledge however suggest that polyomaviruses do not utilise this kind of modification. Moreover, because of a relatively small amount of CpG dinucleotides present in their genomes, they seem to avoid it. The goal of this work is to describe the individual types of these modifications and show their possible importance in the infectious cycle of polyomaviruses. Key words: polyomavirus, epigenetics, histone modification, DNA methylation, CpG dinucleotides
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