Virus Expression Database

GSE84188

Ebolavirus species associated with differential pathogenicity induce distinct host responses in human macrophages

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.

42 Samples

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