Zweerink, Susanne Elisabeth: Investigations into interferon response of novel bat cell cultures upon alphavirus infection. - Bonn, 2013. - Dissertation, Rheinische Friedrich-Wilhelms-Universität Bonn.
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author = {{Susanne Elisabeth Zweerink}},
title = {Investigations into interferon response of novel bat cell cultures upon alphavirus infection},
school = {Rheinische Friedrich-Wilhelms-Universität Bonn},
year = 2013,
month = jun,

note = {Bats have been identified as reservoir for human pathogenic zoonotic viruses like Rabies, Marburg or Henipaviruses. The fact that bats carry viruses without showing clinical symptoms, raised the question if these flying mammals have evolved specific mechanisms to suppress virus replication. To address this question a bat cell culture model was established to investigate the IFN response upon virus infection.
First, cell lines of E. helvum, Epo. buettikoferi and R. aegyptiacus were generated, immortalised and characterized. IFN sensitivity upon viral and artificial IFN-stimuli was analysed by pan-bat IFN real-time RT-PCR assay. To enable comparative analysis of species-specificity and inter-species bioactive IFN secretion the VSV-bioassay was optimized. It was adapted to each cell line and the pan-species IFN enabled with the EC50 factor the determination of relative secreted bioactive IFN concentration.
To determine IFN-signalling, the mRNA expression levels of several IFN stimulated genes (ISGs) were determined with established species-specific real-time RT-PCR assays. These methods enabled comparable studies between bat, murine and human cell lines. The role of bats within the life cycle of arthropod borne alphaviruses is not clear. The prevalence of cross-reactive antibodies was determined by an Immunofluoresence assay, analysing bat sera from several continents and species. In average 5% of the serological samples were found positive which is a comparably low seroprevalence. Interestingly, some Old World bat samples showed exclusive reactivity with New World alphaviruses and vice versa. This cross-reactivity might indicate that the phylogenetic range of alphaviruses in bats could be much higher. In an alphavirus infection model with O´nyong-nyong virus (ONNV) high IFN-induction on mRNA level was detected in all cell lines. Conversely, IFN secretion was reduced. Although IFN-signalling seemed to be more sensitive on mRNA expression level in bat cell lines, this could not be confirmed on protein levels. These results indicated a translational rather than a transcriptional shutoff upon alphavirus infection in bat cell lines. To investigate if these results were ONNV-specific, two additional alphaviruses, Sindbis and Chikungunya virus (SINV and CHIKV), were tested. These infection experiments showed similar results suggesting a general mechanism of alphaviruses to antagonize the IFN response. Interestingly, bat cell lines showed similar IFN response as human cell lines. Generated bat cell lines, designed pan-bat or species-specific real-time RT-PCR assays and the optimized VSV-bioassay altogether enable a detailed analysis of the IFN response to virus infections in bat cell lines, which was especially on the bioactive IFN protein level in this comparable way not possible before.},

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