Sub-Projects of SFB 535
Invasion and Replication Strategies of Pathogenes
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SP B9

Replication and Transcription of Filoviruses


Dr. Elke Mühlberger
Institut für Virologie, Philipps-Universität Marburg

Summary

Members of the Filoviridae family, Ebola (EBOV) and Marburg virus (MARV), are causative agents of viral hemorrhagic fever. With mortality rates as high as 90%, these viruses represent some of the most deadly human pathogens. We are interested in the replication and transcription strategy of these highly pathogenic viruses. It is planned to analyze the structure of filovirus genomic and antigenomic promoters with respect to the recently revealed promoter structure of the EBOV subtype Zaire which follows the rule of six. Subsequent investigations reveal if the replication efficiency of the different filovirus subtypes is influenced by the promoter structure. These analyses are performed by using rescue systems established for MARV and EBOV.
The EBOV subtype Reston is presumably non-pathogenic for humans. Moreover, EBOV Reston proliferates with a lower efficiency in cell culture and seems to be less virulent for monkeys than the highly pathogenic subtpye Zaire suggesting that the replication cycle of EBOV Reston could be delayed. Towards the main objective of analysing the pathogenesis of EBOV Reston we want to investigate whether the replication and transcription rate of EBOV Zaire and EBOV Reston or differences in virus spread are causative for the observed growth impairment. To address this question, quantitative realtime PCR is used to measure the intracellular increase of RNA during the course of infection in infected cells. By measuring the RNA-levels at different time points, we intend to find out if EBOV Reston and EBOV Zaire differ in their replication or transcription efficiency. If the results obtained by RT-PCR indicate that ,indeed, the synthesis of RNA is impaired with the Reston subtype, the structure of the promoter region will be further analyzed. If the replication and transcription rate of EBOV Reston and Zaire shows no detectable differences, it is planned to investigate functional differences of those proteins involved in virus spread by using virus-like particles.
Furthermore, structure-function analyses of selected nucleocapsid proteins are planned. Thus, we are interested in protein interaction and function of the EBOV L protein, the role of MARV VP30 for rescue of recombinant virus, and the characterization of the interferon antagonist VP35. In this context, investigations on the interaction of filoviruses and the type I interferon system are intended.
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