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Antiviral aktive Faktoren der Typ I-Interferonsysteme kleiner Säugetiere
Antragsteller
Professor Dr. Georg Kochs; Professor Dr. Friedemann Weber
Fachliche Zuordnung
Virologie
Förderung
Förderung von 2013 bis 2020
Projektkennung
Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 226373496
The interferon system of mammals represents an important species barrier against invading viruses. Immediately after infection, cells synthesize and secrete type I interferons (IFN-alpha/beta) which bind to their receptor on surrounding cells. This leads to the expression of more than 300 IFN-stimulated genes (ISGs). Several ISG products, among them the so-called Mx proteins, possess antiviral properties, thus controlling intracellular viral replication and spread. It is known that ISGs from different species can have varying antiviral properties. The murine Mx1, for example, specifically inhibits influenza viruses, whereas human MxA targets a broad spectrum of RNA and some DNA viruses. The goal of this project is to characterize the components of the IFN system of bats. Bats are an important zoonotic reservoir. Viruses which are highly virulent for humans can be persistent and asymptomatic in bats. Although it could be key for understanding the differences in virus susceptibility, the IFN system of bats has remained largely uncharacterized. Here, we will investigate the expression of IFN in virus-infected cells from various bat species. Furthermore, we plan to perform a genome-wide transcriptome analysis of virus-infected and IFN-treated cells of a selected bat species, Myotis daubentonii. Candidates for bat ISGs will be cloned and tested for their antiviral activity against a range of viruses. The antiviral Mx protein family will be analyzed in cells covering all bat families in order to analyse co-evolution of the bat IFN system with circulating viruses. Altogether, it is possible that bats possess a special IFN system that allows them to better cope with different kinds of viruses. On the other hand, similarities between the IFN systems of humans and bats could facilitate zoonotic virus transmission between the species without adaptations. The proposed project is aimed at getting first insights into the molecular specialities of the bat antiviral, innate immune response.
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