Kazmierczak, Bernd
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Kazmierczak, Bernd
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Kazmierczak, Bernd
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Item-typ:Veröffentlichung, Untersuchungen zur Suppression der IFN-ß-Induktion durch Proteine des Hepatitis A-Virus, unter besonderer Berücksichtigung des HAV/2B-ProteinsHepatitis A virus antagonizes the innate immune response by inhibition of IRF-3 activation which results in efficient suppression of interferon-β synthesis. This study showed that this ability of the virus is mediated by the viral non-structural proteins 2B and 3ABC. While the processing intermediate 3ABC targets MAVS, 2B might interfere with IRF-3 activation in an indirect manner by associating with intracellular membranes. Deletion of the C-terminal transmembrane domain of 2B results in a loss of function concerning the suppression of IRF 3 activation. In addition to suppression of IRF-3 activation, HAV partially down regulates protein expression which is mediated by the viral non-structural protein 2C. This function of 2C probably depends on its membrane association, too. In the second part of this work could be shown that the suppression of IRF-3 activation and down regulation of protein expression is not due to an adaptation of HAV to growth in cultivated cells because proteins of wildtype viruses show these properties also. These results imply that HAV is able to inhibit IRF-3 activation and partially down regulates protein expression in vivo.Dissertation252 293 - Some of the metrics are blocked by yourconsent settings
Item-typ:Veröffentlichung, Untersuchung der Rolle von IRF-7 bei der Suppression der Hämatopoese durch das Hepatitis A-Virus(2009-11-11); ; ; The interferon regulatory factor 7 (IRF-7) plays an important role in the monocyte (MO)-to-macrophage (MAC) differentiation. This work shows that hepatitis A virus (HAV) suppresses the activation of IRF-7 by blocking its phosphorylation and in the following its nuclear translocalisation. It is hypothesed that this ability of HAV causes the perturbance of the MO-to-MAC maturation observed in HAV infections.Dissertation236 115 - Some of the metrics are blocked by yourconsent settings
Item-typ:Veröffentlichung, Untersuchung zur Einsetzbarkeit der Psoralen-PEO-Biotin Markierung in der DNA-Micorarray Technologie für die Analyse von Starterkulturbakterien und ihren Phagenresistenzgenen(2004-06-02); ; ; Subject of this work was the investigation of the Psoralen-PEO-Biotin labelling method for the direct detection of starter culture bacteria and their phage-resistance genes with the DNA-Microarray-Technology. The use of DNA-Microarray-Technology in industry was up to now limited through different methodological limitations. In this work, the direct detection of genes was established by the combination of DNA-extraction, fragmentation, labelling and hybridization of genomic DNA in an easy to handle and inexpensive protocol.The Psoralen-PEO-Biotin labelling method was established and optimized for genomic DNA in a model system. Various parameters affecting the hybridization efficiency were investigated in this system. Genomic DNA was fragmented with a chemical fragmentation reaction to increase probe accessibility. 73 probes were generated and validated to detect milk bacteria and all phage resistance genes that occur in Lactococcus lactis. The DNA-Microarray was able to detect milk bacteria and phage resistance genes. Phage-resistance genes can be lost and acquired due to the fact that they are plasmid-coded. Only those phage-resistance genes could be directly detected who occurred in more than 16% of the examined starter culture isolates. To increase the sensitivity, two different strategies for signal- and target amplification were embedded into the current protocol. With the Multiplex-PCR in the combination with the created DNA-Microarray all genes were identified correctly. The signal amplification with Tyramide-Cy5 led to signal enhancement for the direct detection of genomic DNA. However, the unambiguous detection of the phage- resistance did not succeed since unspecific signal amplification could not be avoided. The correct proof can certainly be corrected by the optimization of TSA on DNA-Microarrys. So in the near future, it should be possible, to detect low-abundance genes with DNA-Microarrys by the hybridization of genomic DNA without target-amplification.Dissertation248 179