title: Differential transcriptional responses to Ebola and Marburg virus infection in bat and human cells.
abstract: The unprecedented outbreak of Ebola in West Africa resulted in over 28,000 cases and 11,000 deaths, underlining the need for a better understanding of the biology of this highly pathogenic virus to develop specific counter strategies. Two filoviruses, the Ebola and Marburg viruses, result in a severe and often fatal infection in humans. However, bats are natural hosts and survive filovirus infections without obvious symptoms. The molecular basis of this striking difference in the response to filovirus infections is not well understood. We report a systematic overview of differentially expressed genes, activity motifs and pathways in human and bat cells infected with the Ebola and Marburg viruses, and we demonstrate that the replication of filoviruses is more rapid in human cells than in bat cells. We also found that the most strongly regulated genes upon filovirus infection are chemokine ligands and transcription factors. We observed a strong induction of the JAK/STAT pathway, of several genes encoding inhibitors of MAP kinases (DUSP genes) and of PPP1R15A, which is involved in ER stress-induced cell death. We used comparative transcriptomics to provide a data resource that can be used to identify cellular responses that might allow bats to survive filovirus infections.
authors.affiliation: RNA Bioinformatics and High Throughput Analysis, Faculty of Mathematics and Computer Science, Friedrich Schiller University Jena, Leutragraben 1, 07743, Jena, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Hölzer
authors.affiliation: Institute of Virology, Philipps University Marburg, Hans-Meerwein-Str. 2, 35043 Marburg, Germany.|German Center for Infection Research (DZIF), partner site Gießen-Marburg-Langen, Hans-Meerwein Str. 2, 35043, Marburg, Germany.
authors.forename: Verena
authors.initials: V
authors.lastname: Krähling
authors.affiliation: Bioinformatics Group, Department of Computer Science, University of Leipzig, Härtelstraße 16-18, 04107, Leipzig, Germany.
authors.forename: Fabian
authors.initials: F
authors.lastname: Amman
authors.affiliation: RNA Bioinformatics and High Throughput Analysis, Faculty of Mathematics and Computer Science, Friedrich Schiller University Jena, Leutragraben 1, 07743, Jena, Germany.|FLI Leibniz Institute for Age Research, Beutenbergstraße 11, 07745 Jena, Germany.
authors.forename: Emanuel
authors.initials: E
authors.lastname: Barth
authors.affiliation: Transcriptome Bioinformatics, Junior Research Group, Leipzig Research Center for Civilization Diseases, University of Leipzig, Härtelstraße 16-18, 04107, Leipzig, Germany.
authors.forename: Stephan H
authors.initials: SH
authors.lastname: Bernhart
authors.affiliation: Center for non-coding RNA in Technology and Health, University of Copenhagen, Grønnegårdsvej 3, 1870, Frederiksberg C, Denmark.|Department of Veterinary Clinical and Animal Sciences, University of Copenhagen, Grønnegårdsvej 3, 1870, Frederiksberg C, Denmark.
authors.forename: Victor A O
authors.initials: VA
authors.lastname: Carmelo
authors.affiliation: RNA Bioinformatics and High Throughput Analysis, Faculty of Mathematics and Computer Science, Friedrich Schiller University Jena, Leutragraben 1, 07743, Jena, Germany.|Institute of Virology, Philipps University Marburg, Hans-Meerwein-Str. 2, 35043 Marburg, Germany.
authors.forename: Maximilian
authors.initials: M
authors.lastname: Collatz
authors.affiliation: Transcriptome Bioinformatics, Junior Research Group, Leipzig Research Center for Civilization Diseases, University of Leipzig, Härtelstraße 16-18, 04107, Leipzig, Germany.
authors.forename: Gero
authors.initials: G
authors.lastname: Doose
authors.affiliation: Theoretical Biochemistry Group, Institute of Theoretical Chemistry, University of Vienna, Währingerstraße 17, 1090, Vienna, Austria.|Bioinformatics Group, Department of Computer Science, University of Freiburg, Georges-Köhler-Allee 106, 79110, Freiburg, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Eggenhofer
authors.affiliation: Research Group Theoretical Systems Biology, Department of Bioinformatics, Friedrich Schiller University Jena, Ernst-Abbe-Platz 2, 07743, Jena, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Ewald
authors.affiliation: Bioinformatics Group, Department of Computer Science, University of Leipzig, Härtelstraße 16-18, 04107, Leipzig, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Fallmann
authors.affiliation: Institute of Computer Science, Martin-Luther University Halle-Wittenberg, Von-Seckendorff-Platz 1, 06120, Halle/Saale, Germany.|Department of Soil Ecology, UFZ - Helmholtz Centre for Environmental Research, Theodor-Lieser-Str. 4, 06120, Halle/Saale, Germany.|German Centre for Integrative Biodiversity Research (iDiv) Halle-Jena-Leipzig, Deutscher Platz 5e, 04103, Leipzig, Germany.
authors.forename: Lasse M
authors.initials: LM
authors.lastname: Feldhahn
authors.affiliation: RNA Bioinformatics and High Throughput Analysis, Faculty of Mathematics and Computer Science, Friedrich Schiller University Jena, Leutragraben 1, 07743, Jena, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Fricke
authors.affiliation: Research Group Theoretical Systems Biology, Department of Bioinformatics, Friedrich Schiller University Jena, Ernst-Abbe-Platz 2, 07743, Jena, Germany.
authors.forename: Juliane
authors.initials: J
authors.lastname: Gebauer
authors.affiliation: Biozentrum, University of Basel, Klingelbergstraße 50/70, CH-4056, Basel, Switzerland.
authors.forename: Andreas J
authors.initials: AJ
authors.lastname: Gruber
authors.affiliation: RNA Bioinformatics and High Throughput Analysis, Faculty of Mathematics and Computer Science, Friedrich Schiller University Jena, Leutragraben 1, 07743, Jena, Germany.|Chair of Bioinformatics, Faculty of Mathematics and Computer Science, Friedrich Schiller University Jena, Ernst-Abbe-Platz 2, 07743, Jena, Germany.
authors.forename: Franziska
authors.initials: F
authors.lastname: Hufsky
authors.affiliation: Bioinformatics Group, Department of Computer Science, University of Leipzig, Härtelstraße 16-18, 04107, Leipzig, Germany.|Junior Professorship for Computational EvoDevo, Bioinformatics, Department of Computer Science, University of Leipzig, Härtelstraße 16-18, 04107, Leipzig, Germany.
authors.forename: Henrike
authors.initials: H
authors.lastname: Indrischek
authors.affiliation: TFome Research Group, Bioinformatics Group, Interdisciplinary Center of Bioinformatics, Department of Computer Science, University of Leipzig, Härtelstraße 16-18, 04107, Leipzig, Germany.|Paul-Flechsig-Institute for Brain Research, University of Leipzig, Jahnallee 54, 04109, Leipzig, Germany.
authors.forename: Sabina
authors.initials: S
authors.lastname: Kanton
authors.affiliation: Leibniz Institute for Natural Product Research and Infection Biology Hans Knöll Institute (HKI), Systems Biology and Bioinformatics, Beutenbergstraße 11a, 07745, Jena, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Linde
authors.affiliation: RNA Bioinformatics and High Throughput Analysis, Faculty of Mathematics and Computer Science, Friedrich Schiller University Jena, Leutragraben 1, 07743, Jena, Germany.|Institute of Virology, Philipps University Marburg, Hans-Meerwein-Str. 2, 35043 Marburg, Germany.
authors.forename: Nelly
authors.initials: N
authors.lastname: Mostajo
authors.affiliation: Theoretical Biochemistry Group, Institute of Theoretical Chemistry, University of Vienna, Währingerstraße 17, 1090, Vienna, Austria.
authors.forename: Roman
authors.initials: R
authors.lastname: Ochsenreiter
authors.affiliation: RNA Bioinformatics and High Throughput Analysis, Faculty of Mathematics and Computer Science, Friedrich Schiller University Jena, Leutragraben 1, 07743, Jena, Germany.
authors.forename: Konstantin
authors.initials: K
authors.lastname: Riege
authors.affiliation: Bioinformatics Group, Department of Computer Science, University of Leipzig, Härtelstraße 16-18, 04107, Leipzig, Germany.|Department of Bioanalytical Ecotoxicology, UFZ-Helmholtz Centre for Environmental Research, Leipzig, Germany.
authors.forename: Lorena
authors.initials: L
authors.lastname: Rivarola-Duarte
authors.affiliation: RNA Bioinformatics and High Throughput Analysis, Faculty of Mathematics and Computer Science, Friedrich Schiller University Jena, Leutragraben 1, 07743, Jena, Germany.|Bioinformatics Group, Department of Computer Science, University of Leipzig, Härtelstraße 16-18, 04107, Leipzig, Germany.|Doctoral School of Science and Technology, AZM Center for Biotechnology Research, Lebanese University, Tripoli, Lebanon.|TRON - Translational Oncology at the University Medical Center of the Johannes Gutenberg University Mainz gGmbH, Mainz, Germany.
authors.forename: Abdullah H
authors.initials: AH
authors.lastname: Sahyoun
authors.affiliation: Bioinformatics Group, Department of Computer Science, University of Freiburg, Georges-Köhler-Allee 106, 79110, Freiburg, Germany.
authors.forename: Sita J
authors.initials: SJ
authors.lastname: Saunders
authors.affiliation: Center for non-coding RNA in Technology and Health, University of Copenhagen, Grønnegårdsvej 3, 1870, Frederiksberg C, Denmark.|Department of Veterinary Clinical and Animal Sciences, University of Copenhagen, Grønnegårdsvej 3, 1870, Frederiksberg C, Denmark.
authors.forename: Stefan E
authors.initials: SE
authors.lastname: Seemann
authors.affiliation: Theoretical Biochemistry Group, Institute of Theoretical Chemistry, University of Vienna, Währingerstraße 17, 1090, Vienna, Austria.
authors.forename: Andrea
authors.initials: A
authors.lastname: Tanzer
authors.affiliation: RNA Bioinformatics and High Throughput Analysis, Faculty of Mathematics and Computer Science, Friedrich Schiller University Jena, Leutragraben 1, 07743, Jena, Germany.|Institute of Virology, Philipps University Marburg, Hans-Meerwein-Str. 2, 35043 Marburg, Germany.|Chair of Bioinformatics, Faculty of Mathematics and Computer Science, Friedrich Schiller University Jena, Ernst-Abbe-Platz 2, 07743, Jena, Germany.
authors.forename: Bertram
authors.initials: B
authors.lastname: Vogel
authors.affiliation: RNA Bioinformatics and High Throughput Analysis, Faculty of Mathematics and Computer Science, Friedrich Schiller University Jena, Leutragraben 1, 07743, Jena, Germany.|Institute of Aquaculture, University of Stirling, Stirling FK9 4LA, Scotland, U.K.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Wehner
authors.affiliation: Theoretical Biochemistry Group, Institute of Theoretical Chemistry, University of Vienna, Währingerstraße 17, 1090, Vienna, Austria.|Medical University of Vienna, Center for Anatomy and Cell Biology, Währingerstraße 13, 1090, Vienna, Austria.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Wolfinger
authors.affiliation: Center for non-coding RNA in Technology and Health, University of Copenhagen, Grønnegårdsvej 3, 1870, Frederiksberg C, Denmark.|Bioinformatics Group, Department of Computer Science, University of Freiburg, Georges-Köhler-Allee 106, 79110, Freiburg, Germany.|Centre for Biological Signalling Studies (BIOSS), University of Freiburg, Freiburg, Germany.
authors.forename: Rolf
authors.initials: R
authors.lastname: Backofen
authors.affiliation: Center for non-coding RNA in Technology and Health, University of Copenhagen, Grønnegårdsvej 3, 1870, Frederiksberg C, Denmark.|Department of Veterinary Clinical and Animal Sciences, University of Copenhagen, Grønnegårdsvej 3, 1870, Frederiksberg C, Denmark.
authors.forename: Jan
authors.initials: J
authors.lastname: Gorodkin
authors.affiliation: Institute of Computer Science, Martin-Luther University Halle-Wittenberg, Von-Seckendorff-Platz 1, 06120, Halle/Saale, Germany.|Department of Soil Ecology, UFZ - Helmholtz Centre for Environmental Research, Theodor-Lieser-Str. 4, 06120, Halle/Saale, Germany.
authors.forename: Ivo
authors.initials: I
authors.lastname: Grosse
authors.affiliation: Center for non-coding RNA in Technology and Health, University of Copenhagen, Grønnegårdsvej 3, 1870, Frederiksberg C, Denmark.|Theoretical Biochemistry Group, Institute of Theoretical Chemistry, University of Vienna, Währingerstraße 17, 1090, Vienna, Austria.|Research group Bioinformatics and Computational Biology, Faculty of Computer Science, University of Vienna, Währingerstraße 29, 1090, Vienna, Austria.
authors.forename: Ivo
authors.initials: I
authors.lastname: Hofacker
authors.affiliation: Transcriptome Bioinformatics, Junior Research Group, Leipzig Research Center for Civilization Diseases, University of Leipzig, Härtelstraße 16-18, 04107, Leipzig, Germany.
authors.forename: Steve
authors.initials: S
authors.lastname: Hoffmann
authors.affiliation: Research Group Medical Systems Biology, Institute for Experimental Medicine, Christian-Albrechts-University Kiel, Brunswiker Str. 10, 24105, Kiel, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Kaleta
authors.affiliation: Bioinformatics Group, Department of Computer Science, University of Leipzig, Härtelstraße 16-18, 04107, Leipzig, Germany.|Center for non-coding RNA in Technology and Health, University of Copenhagen, Grønnegårdsvej 3, 1870, Frederiksberg C, Denmark.
authors.forename: Peter F
authors.initials: PF
authors.lastname: Stadler
authors.affiliation: Institute of Virology, Philipps University Marburg, Hans-Meerwein-Str. 2, 35043 Marburg, Germany.|German Center for Infection Research (DZIF), partner site Gießen-Marburg-Langen, Hans-Meerwein Str. 2, 35043, Marburg, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Becker
authors.affiliation: RNA Bioinformatics and High Throughput Analysis, Faculty of Mathematics and Computer Science, Friedrich Schiller University Jena, Leutragraben 1, 07743, Jena, Germany.|FLI Leibniz Institute for Age Research, Beutenbergstraße 11, 07745 Jena, Germany.
authors.forename: Manja
authors.initials: M
authors.lastname: Marz
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002685:Chiroptera; D029043:Ebolavirus / Q000378:metabolism*; D005786:Gene Expression Regulation; D019142:Hemorrhagic Fever, Ebola / Q000378:metabolism*; D006801:Humans; D008379:Marburg Virus Disease / Q000378:metabolism*; D029024:Marburgvirus / Q000378:metabolism*; D015398:Signal Transduction; D014158:Transcription, Genetic