Charakterisierung der Eigenschaften der nichtkodierenden Enden der Genomsegmente des Oropouche-Virus und ihre Bedeutung für die virale Transkription/Replikation sowie die Interaktion mit dem Typ-I-Interferonsystem

Characterisation of non-coding regions of the OROV genome segments and their relevance for viral transcription/replication as well as interaction with the type-I interferon system

by Katharina Schnülle
Doctoral thesis
Date of Examination:2013-08-06
Date of issue:2013-07-25
Advisor:Dr. Martin Spiegel
Referee:Prof. Dr. Frank Torsten Hufert
Referee:Prof. Dr. Lutz Walter
Referee:Prof. Dr. Martin Oppermann
Persistent Address: http://dx.doi.org/10.53846/goediss-3951

 

 

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Abstract

English

The Oropouche virus (OROV) is a RNA virus from the Bunyaviridae family. Its genome consists of a single-stranded negative sense RNA. The Oropouche fever is caused by this virus and is most common in Central and South America. Moreover it is the second most prevalent arboviral disease after Dengue fever in Brazil and there are no therapeutical options, yet. To guarantee efficient viral replication viruses within this family encode for a non-structural protein (NSs), which operates in an interferon antagonistic function by suppressing the host cell´s RNAP II mediated transcription. Because of this mechanism there is no type-I interferon induction after virus infection. In this thesis I found that through their triphosphate modification at the 5`end the OROV RNA genome segments itself are potent inducers of the interferon system. Moreover type-I interferon is able to sufficiently block OROV replication. Therefore the virus needs an interferon antagonist for efficient replication. The intracellular targets of the NSs protein are still unknown but due to these results their distribution seems to be intranuclear. In addition I established an OROV minireplicon system. Sequence analyses of the viral polymerase und the non-coding ends revealed that the published reference sequences for both are not correct. Especially for the non-coding ends not only the nucleotide sequence itself but the deduced secondary structure seems to be essential for their function.
Keywords: Oropouche virus; minireplicon system; Bunyaviridae
Schlagwörter: Oropouche-Virus; Minireplikon-System; Bunyaviren
 
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