Charakterisierung der TypI-Interferon-antagonistischen Aktivität der humanpathogenen Orbiviren Tribec-Virus und Kemerovo-Virus

Berndt, Christian Philipp

dc.contributor.advisor	Hufert, Frank Torsten Prof. Dr.
dc.contributor.author	Berndt, Christian Philipp
dc.date.accessioned	2015-01-20T10:12:33Z
dc.date.available	2015-02-11T23:50:11Z
dc.date.issued	2015-01-20
dc.identifier.uri	http://hdl.handle.net/11858/00-1735-0000-0022-5D87-9
dc.identifier.uri	http://dx.doi.org/10.53846/goediss-4853
dc.language.iso	deu	de
dc.rights.uri	http://creativecommons.org/licenses/by-nc-nd/3.0/
dc.subject.ddc	610	de
dc.title	Charakterisierung der TypI-Interferon-antagonistischen Aktivität der humanpathogenen Orbiviren Tribec-Virus und Kemerovo-Virus	de
dc.type	doctoralThesis	de
dc.title.translated	Characterization of type I IFN antagonistic activity of the human pathogenic Orbiviruses Tribec virus and Kemerovo virus	de
dc.contributor.referee	Hufert, Frank Torsten Prof. Dr.
dc.date.examination	2015-02-04
dc.description.abstracteng	Tribec- (TRBV) as well as Kemerovo virus (KEMV) are sheep tick (Ixodes persulcatus and Ixodes ricinus) transmitted Orbiviruses (Reoviridae family). They are under suspicion of causing inflammations of the cerebrospinal nervous system in humans and other mammals. Since their discovery in the west Siberian Tribec mountain range in the 1960th, these viruses could be found in huge parts of Europe. There is only few, which is known about the distinct pathomechanisms. Therefore the present work is attended to the humanpathogenic potential and the underlying pathomechanisms of both viruses. Within the present work it could be shown that TRBV and KEMV nearly completely inhibit IFN-beta induction of human kidney cells (cell line HEK293). Illustrated by cell growth curves a strong cytopathogen effect could be observed. Because of the inhibition of IFN-beta induction, even in cells which are coinfected with the interferon-inducing RVFV Clone 13, it seems to be about an active way of inhibiting type I IFN system. Besides a stronger cytopathogen effect could be found in coinfected cells than in only RVFV Clone 13 infected cells. Furthermore it could be shown that establishment of an antiviral state by cell-treatment with IFN-alpha results in a normalization of cell-growth. Because of that it is presumable that this active inhibition of type I IFN system plays a crucial role for the quality of TRBV- resp. KEMV-infection. Immunofluorescence tests could detect an induction of apoptosis, increasing by proceed of time. Regarding this, treatment with the pan-caspase-inhibitor Z-VAD-FMK could not prevent that. Therefore it could be caspase-independent signaling pathways which are responsible for apoptosis-induction. Again promoterstudies could attest, that TRBV-segment 9 is responsible for the major part of inhibition of the IFN-β-promoter. For the first time it could be shown that none of the single open reading frames (helicase as well as ORFXa-, -b- or -c-coding regions) are coding for a viral interferon-antagonists. Moreover TRBV-segments 2, 3 and 4 habe been investigated. While segment 2 (coding for VP2) might play a role in interferon-antagonism, segments 3 and 4 show no effect concerning inhibition of the IFN-beta-promoter. Regarding KEMV it could be detected for the first time that it is presumably the viral genomic segment 9 as well which leads to the inhibition of the human IFN-beta-promoter.	de
dc.contributor.coReferee	Oppermann, Martin Prof. Dr.
dc.subject.ger	TRBV	de
dc.subject.ger	KEMV	de
dc.subject.ger	Tribec	de
dc.subject.ger	Kemerovo	de
dc.subject.ger	Interferon	de
dc.subject.ger	Helikase	de
dc.subject.ger	ORFX	de
dc.subject.eng	TRBV	de
dc.subject.eng	KEMV	de
dc.subject.eng	tribec	de
dc.subject.eng	kemerovo	de
dc.subject.eng	interferon	de
dc.subject.eng	helicase	de
dc.subject.eng	ORFX	de
dc.identifier.urn	urn:nbn:de:gbv:7-11858/00-1735-0000-0022-5D87-9-5
dc.affiliation.institute	Medizinische Fakultät	de
dc.subject.gokfull	Medizin (PPN619874732)	de
dc.subject.gokfull	Medizinische Mikrobiologie / Medizinische Virologie / Medizinische Mykologie / Infektionskrankheiten / Hygiene / Impfung / Parasitologie / Tropenmedizin - Allgemein- und Gesamtdarstellungen (PPN619875356)	de
dc.description.embargoed	2015-02-11
dc.identifier.ppn	815825765

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