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.
Sci Rep. 2016 Oct 7;6:34589. doi: 10.1038/srep34589.
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.
西非史无前例的埃博拉疫情导致超过 28000 例病例和 11000 人死亡，这凸显了需要更好地了解这种高致病性病毒的生物学特性，以制定特定的对抗策略。两种丝状病毒，埃博拉病毒和马尔堡病毒，会导致人类严重且常常致命的感染。然而，蝙蝠是其自然宿主，能够在没有明显症状的情况下存活丝状病毒感染。对于这种对丝状病毒感染反应的显著差异的分子基础还不是很清楚。我们报告了对感染埃博拉病毒和马尔堡病毒的人类细胞和蝙蝠细胞中差异表达基因、活性基序和途径的系统概述，并且我们证明丝状病毒在人类细胞中的复制速度比在蝙蝠细胞中更快。我们还发现，丝状病毒感染后最强调节的基因是趋化因子配体和转录因子。我们观察到 JAK/STAT 途径、几个编码丝裂原活化蛋白激酶抑制剂（DUSP 基因）和参与 ER 应激诱导细胞死亡的 PPP1R15A 的强烈诱导。我们使用比较转录组学提供了一个可用于识别可能使蝙蝠能够存活丝状病毒感染的细胞反应的数据集。
