Differential transcriptional responses to Ebola and Marburg virus infection in bat and human cells

被引:35
作者
Hoelzer, Martin [1 ]
Kraehling, Verena [2 ,3 ]
Amman, Fabian [4 ]
Barth, Emanuel [1 ,5 ]
Bernhart, Stephan H. [6 ]
Carmelo, Victor A. O. [7 ,8 ]
Collatz, Maximilian [1 ,2 ]
Doose, Gero
Eggenhofer, Florian [10 ]
Ewald, Jan [11 ]
Fallmann, Joerg [4 ]
Feldhahn, Lasse M. [12 ,13 ,14 ]
Fricke, Markus [1 ]
Gebauer, Juliane [11 ]
Gruber, Andreas J. [15 ]
Hufsky, Franziska [16 ]
Indrischek, Henrike [4 ,17 ]
Kanton, Sabina [18 ,19 ]
Linde, Joerg [20 ]
Mostajo, Nelly [1 ,2 ]
Ochsenreiter, Roman [9 ]
Riege, Konstantin [1 ]
Rivarola-Duarte, Lorena [4 ,21 ]
Sahyoun, Abdullah H. [1 ,4 ,22 ,23 ]
Saunders, Sita J. [10 ]
Seemann, Stefan E. [8 ]
Tanzer, Andrea [9 ]
Vogel, Bertram [1 ,2 ,16 ]
Wehner, Stefanie [1 ,24 ]
Wolfinger, Michael T. [9 ,25 ]
Backofen, Rolf [10 ,26 ]
Gorodkin, Jan [7 ,8 ]
Grosse, Ivo [12 ,13 ]
Hofacker, Ivo [9 ,27 ]
Hoffmann, Steve [6 ]
Kaleta, Christoph [28 ]
Stadler, Peter F. [4 ,7 ]
Becker, Stephan [2 ,3 ]
Marz, Manja [1 ,5 ]
机构
[1] Univ Jena, Fac Math & Comp Sci, RNA Bioinformat & High Throughput Anal, Leutragraben 1, D-07743 Jena, Germany
[2] Philipps Univ Marburg, Inst Virol, Hans Meerwein Str 2, D-35043 Marburg, Germany
[3] German Ctr Infect Res DZIF, Partner Site Gissen Marburg Langen, D-35043 Marburg, Germany
[4] Univ Leipzig, Dept Comp Sci, Bioinformat Grp, Hartelstr 16-18, D-04107 Leipzig, Germany
[5] FLI Leibniz Inst Age Res, Beutenbergstr 11, D-07745 Jena, Germany
[6] Univ Leipzig, Leipzig Res Ctr Civilizat Dis, Jr Res Grp, Transcriptome Bioinformat, Hartelstr 16-18, D-04107 Leipzig, Germany
[7] Univ Copenhagen, Ctr noncoding RNA Technol & Hlth, Gronnegardsvej 3, DK-1870 Frederiksberg C, Denmark
[8] Univ Copenhagen, Dept Vet Clin & Anim Sci, Gronnegardsvej 3, DK-1870 Frederiksberg C, Denmark
[9] Univ Vienna, Inst Theoret Chem, Theoret Biochem Grp, Wahringerstr 17, A-1090 Vienna, Austria
[10] Univ Freiburg, Dept Comp Sci, Bioinformat Grp, Georges Kohler Allee 106, D-79110 Freiburg, Germany
[11] Univ Jena, Dept Bioinformat, Res Grp Theoret Syst Biol, Ernst Abbe Pl 2, D-07743 Jena, Germany
[12] Univ Halle Wittenberg, Inst Comp Sci, Von Seckendorff Pl 1, D-06120 Halle, Germany
[13] UFZ Helmholtz Ctr Environm Res, Dept Soil Ecol, Theodor Lieser Str 4, D-06120 Halle, Germany
[14] German Ctr Integrat Biodivers Res iDiv, Deutsch Pl 5E, D-04103 Leipzig, Germany
[15] Univ Basel, Biozentrum, Klingelbergstr 50-70, CH-4056 Basel, Switzerland
[16] Univ Jena, Chair Bioinformat, Fac Math & Comp Sci, Ernst Abbe Pl 2, D-07743 Jena, Germany
[17] Univ Leipzig, Dept Comp Sci, Jr Professorship Computat EvoDevo, Bioinformat, Hartelstr 16-18, D-04107 Leipzig, Germany
[18] Univ Leipzig, Dept Comp Sci, TFome Res Grp, Bioinformat Grp,Interdisciplinary Ctr Bioinformat, Hartelstr 16-18, D-04107 Leipzig, Germany
[19] Univ Leipzig, Paul Flechsig Inst Brain Res, Jahnallee 54, D-04109 Leipzig, Germany
[20] Leibniz Inst Nat Product Res & Infect Biol, Hans Knoll Inst HKI, Syst Biol & Bioinformat, Beutenbergstr 11A, D-07745 Jena, Germany
[21] UFZ Helmholtz Ctr Environm Res, Dept Bioanalyt Ecotoxicol, Leipzig, Germany
[22] Lebanese Univ, Doctoral Sch Sci & Technol, AZM Ctr Biotechnol Res, Tripoli, Lebanon
[23] Johannes Gutenberg Univ Mainz gGmbH, Univ Med Ctr, TRON Translat Oncol, Mainz, Germany
[24] Univ Stirling, Inst Aquaculture, Stirling FK9 4LA, Scotland
[25] Med Univ Vienna, Ctr Anat & Cell Biol, Wahringerstr 13, A-1090 Vienna, Austria
[26] Univ Freiburg, Ctr Biol Signalling Studies BIOSS, Freiburg, Germany
[27] Univ Vienna, Res Grp Bioinformat & Computat Biol, Fac Comp Sci, Wahringerstr 29, A-1090 Vienna, Austria
[28] Univ Kiel, Inst Expt Med, Res Grp Med Syst Biol, Brunswiker Str 10, D-24105 Kiel, Germany
基金
奥地利科学基金会;
关键词
VP35; PROTEIN; KARYOPHERIN ALPHA-1; HEMORRHAGIC-FEVER; GENE-EXPRESSION; RNA; PATHWAY; SUPPRESSION; ACTIVATION; RECEPTOR; PHOSPHATASES;
D O I
10.1038/srep34589
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
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页数:16
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