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Projekt
Investigations of filovirus propagation and cellular defense mechanisms against filoviruses in the reservoir host Rousettus aegyptiacus and other fruit bat species
Antragsteller
Professor Dr. Stephan Becker
Fachliche Zuordnung
Virologie
Förderung
Förderung von 2013 bis 2016
Projektkennung
Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 226375906
Marburg virus (MARV) and Ebola viruses (EBOV), both members of the family Filoviridae, reside in fruit bats in Central Africa and cause sporadic outbreaks in the human population. Filoviral infections in humans lead to a severe hemorrhagic fever with high case-fatality rates, in contrast, fruit bats, the natural reservoir for filoviruses do not seem to show symptoms. Primary target cells for filoviruses in humans are monocytes, macrophages and dendritic cells. Impairment of their function in innate and adaptive immunity leads to massive cytokine secretion and severity of the disease caused by filoviruses. Currently it is not known whether fruit bat derived monocytes, macrophages and dendritic cells are susceptible to filovirus infection and if they play a decisive role during the course of infection.Distinct fruit bat species are described as the potential reservoir for EBOV and MARV. EBOVspecific antibodies were detected in three different fruit bat species: the Hammer-headed Bat, Franquet’s Epauletted Fruit Bat and Little Collared Fruit Bat. MARV-specific RNA and antibodies were found in another fruit bat species the Egyptian Fruit Bat and so far, this is the only species from which infectious MARV has been isolated. MARV and EBOV proliferate unequally well in cells from the Egyptian Fruit Bat. Therefore we presume that virus-specific differences determine their capability to replicate in a specific fruit bat cell.The type-I-interferon (IFN) system is the first effective cellular defense mechanism against viruses and most viruses developed counter strategies that inhibit the IFN system to allow viral replication. Species-specific differences in the capability of viral proteins to inhibit the IFN response can be relevant for the adaptation of viruses to a new host. Nothing is known so far on how the filoviral IFN antagonists (VP35, VP40 and VP24) control the IFN system of fruit bats and whether speciesspecific differences might contribute to reduced pathogenicity of the virus in the reservoir host in comparison to the recipient host.Taken together, very little is known about the differences between reservoir host and recipient species in terms of their ability to replicate or restrict filoviruses. These differences, however, are important to understand on the one hand the pathogenicity of filoviruses in humans and on the other hand the immune system of bats that are able to propagate many viruses that induce severe diseases in men. We would like to investigate (i) the response of immortalized and primary cells of fruit bats to filovirus infection, (ii) the propagation of different virus strains in fruit bat cells, (iii) cellular defense mechanisms against filoviruses in fruit bat derived cells.
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