Virus Expression Database
Submitted by Angela Rasmussen (Columbia University, USA) on Jul 08 2016
Platform: ngs – Illumina NextSeq 500 (Homo sapiens)
Pubmed: 28331091
Summary Highly pathogenic Zaire ebolavirus (EBOV) infection is associated with a dysregulated immune response and high levels of cytokines and chemokines are observed in fatal human cases. . In stark contrast Reston ebolavirus (RESTV) might be non-pathogenic for humans yet the underlying mechanisms determining pathogenicity for different Ebola viruses are not understood. In this study we investigate antiviral immune responses in EBOV- and RESTV- infected primary human monocyte-derived macrophages (MDM). We provide evidence that increased pathogenicity of the highly pathogenic EBOV is associated with a strong activation of host responses from infected MDM. The observed cytokine response after EBOV infection is strikingly similar to LPS-mediated immune signatures however EBOV caused significant induction of the interferon response in addition. In contrast we show that the low pathogenic RESTV fails to elicit significant immune responses in infected MDM. These results demonstrate a correlation of pathogenicity and excessive MDM activation for different Ebola virus species. Interaction of the viral glycoprotein (GP) with Toll-like receptor 4 (TLR4) leading to activation of NF_B signaling is responsible for this effect rather than differences in replication or blocking of immune signaling. We demonstrate that inhibition of TLR4 is able to abolish EBOV-GP mediated NF_B activation which might offer the possibility to develop targeted treatments for EBOV limiting the extreme immune response that seems to be detrimental to the host.
| ID | Title | Cell Type | Timepoint | Reported Virus | Virus Species | Exclusion Reason |
|---|---|---|---|---|---|---|
| GSM2228762 | Donor9_MOCK_6H | macrophage  |
6 hrs | mock | Uninfected | |
| GSM2228763 | Donor9_LPS_6H | macrophage |
6 hrs | LPS | Uninfected | |
| GSM2228764 | Donor9_EBOV_6H | macrophage |
6 hrs | EBOV Kikwit-95 | Zaire ebolavirus | |
| GSM2228765 | Donor9_RESTV_6H | macrophage |
6 hrs | RESTV Pennsylvania | Reston ebolavirus | |
| GSM2228766 | Donor9_MOCK_1D | macrophage |
1 day | mock | Uninfected | |
| GSM2228767 | Donor9_LPS_1D | macrophage |
1 day | LPS | Uninfected | |
| GSM2228768 | Donor9_EBOV_1D | macrophage |
1 day | EBOV Kikwit-95 | Zaire ebolavirus | |
| GSM2228769 | Donor9_RESTV_1D | macrophage |
1 day | RESTV Pennsylvania | Reston ebolavirus | |
| GSM2228770 | Donor9_MOCK_2D | macrophage |
2 days | mock | Uninfected | |
| GSM2228771 | Donor9_LPS2D | macrophage |
2 days | LPS | Uninfected | |
| GSM2228772 | Donor9_EBOV-2D | macrophage |
2 days | EBOV Kikwit-95 | Zaire ebolavirus | |
| GSM2228773 | Donor9_RESTV-2D | macrophage |
2 days | RESTV Pennsylvania | Reston ebolavirus | |
| GSM2228774 | Donor9_EBOV-1D_LPS-6H | macrophage |
1 day | EBOV Kikwit-95 | Zaire ebolavirus | Extra interventions +LPS 6hrs |
| GSM2228775 | Donor9_RESTV-1D_LPS-6H | macrophage |
1 day | RESTV Pennsylvania | Reston ebolavirus | Extra interventions +LPS 6hrs |
| GSM2228776 | Donor10_MOCK-6H | macrophage |
6 hrs | mock | Uninfected | |
| GSM2228777 | Donor10_LPS-6H | macrophage |
6 hrs | LPS | Uninfected | |
| GSM2228778 | Donor10_EBOV-6H | macrophage |
6 hrs | EBOV Kikwit-95 | Zaire ebolavirus | |
| GSM2228779 | Donor10_RESTV-6H | macrophage |
6 hrs | RESTV Pennsylvania | Reston ebolavirus | |
| GSM2228780 | Donor10_MOCK-1D | macrophage |
1 day | mock | Uninfected | |
| GSM2228781 | Donor10_LPS-1D | macrophage |
1 day | LPS | Uninfected | |
| GSM2228782 | Donor10_EBOV-1D | macrophage |
1 day | EBOV Kikwit-95 | Zaire ebolavirus | |
| GSM2228783 | Donor10_RESTV-1D | macrophage |
1 day | RESTV Pennsylvania | Reston ebolavirus | |
| GSM2228784 | Donor10_MOCK-2D | macrophage |
2 days | mock | Uninfected | |
| GSM2228785 | Donor10_LPS-2D | macrophage |
2 days | LPS | Uninfected | |
| GSM2228786 | Donor10_EBOV-2D | macrophage |
2 days | EBOV Kikwit-95 | Zaire ebolavirus | |
| GSM2228787 | Donor10_RESTV-2D | macrophage |
2 days | RESTV Pennsylvania | Reston ebolavirus | |
| GSM2228788 | Donor10_EBOV-1D_LPS 6H | macrophage |
1 day | EBOV Kikwit-95 | Zaire ebolavirus | Extra interventions +LPS 6hrs |
| GSM2228789 | Donor10_RESTV-1D_LPS 6H | macrophage |
1 day | RESTV Pennsylvania | Reston ebolavirus | Extra interventions +LPS 6hrs |
| GSM2228790 | Donor11_MOCK-1D_6H | macrophage |
6 hrs | mock | Uninfected | |
| GSM2228791 | Donor11_LPS-1D_6H | macrophage |
6 hrs | LPS | Uninfected | |
| GSM2228792 | Donor11_EBOV_6H | macrophage |
6 hrs | EBOV Kikwit-95 | Zaire ebolavirus | |
| GSM2228793 | Donor11_RESTV_6H | macrophage |
6 hrs | RESTV Pennsylvania | Reston ebolavirus | |
| GSM2228794 | Donor11_MOCK_1D | macrophage |
1 day | mock | Uninfected | |
| GSM2228795 | Donor11_LPS1D | macrophage |
1 day | LPS | Uninfected | |
| GSM2228796 | Donor11_EBOV_1D | macrophage |
1 day | EBOV Kikwit-95 | Zaire ebolavirus | |
| GSM2228797 | Donor11_RESTV_1D | macrophage |
1 day | RESTV Pennsylvania | Reston ebolavirus | |
| GSM2228798 | Donor11_MOCK_2D | macrophage |
2 days | mock | Uninfected | |
| GSM2228799 | Donor11_LPS_2D | macrophage |
2 days | LPS | Uninfected | |
| GSM2228800 | Donor11_EBOV_2D | macrophage |
2 days | EBOV Kikwit-95 | Zaire ebolavirus | |
| GSM2228801 | Donor11_RESTV_2D | macrophage |
2 days | RESTV Pennsylvania | Reston ebolavirus | |
| GSM2228802 | Donor11_EBOV_1D_LPS_6H | macrophage |
1 day | EBOV Kikwit-95 | Zaire ebolavirus | Extra interventions +LPS 6hrs |
| GSM2228803 | Donor11_RESTV_1D_LPS_6H | macrophage |
1 day | RESTV Pennsylvania | Reston ebolavirus | Extra interventions +LPS 6hrs |