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.
Highlights
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
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
immunofluorescence analysis (IFA) of the Marburg virus (MARV) and Ebola virus (EBOV) nucleoproteins revealed that a multiplicity of infection (MOI) of 3 was sufficient to initially infect a high percentage of cells (90% of human and bat cells infected with EBOV, 70% of bat cells and 99% of human cells infected with MARV, Fig. 1C/D)
Summary
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. The Ebola and Marburg viruses, result in a severe and often fatal infection in humans. EBOV and Marburg virus (MARV) are closely related filoviruses, with a nucleotide identity of 49.5% They contain single-stranded RNA genomes with a negative orientation that are approximately 19 kb in size and encode seven structural proteins[1]. We explored the cellular regulatory response mechanisms by sequencing the full transcriptomes of immortalized cells of human and bat origin at three different time points post infection (p.i.). We provide a systematic report on (1) a genome-wide analysis of EBOV, MARV, human, and bat transcripts, as well as (2) single genes that show strong differential regulation, (3) the regulatory transcription factors, and (4) the corresponding pathways that are involved in the response to EBOV and MARV infections. We focus on the transcriptional differences and similarities between EBOV- and MARV-infected human and bat cells
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