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[h=1]A Systems Approach Reveals MAVS Signaling in Myeloid Cells as Critical for Resistance to Ebola Virus in Murine Models of Infection[/h] Mukta Dutta[SUP]5[/SUP]
, Shelly J. Robertson[SUP]5[/SUP]
, Atsushi Okumura
, Dana P. Scott
, Jean Chang
, Jeffrey M. Weiss
, Gail L. Sturdevant
, Friederike Feldmann
, Elaine Haddock
, Abhilash I. Chiramel
, Sanket S. Ponia
, Jonathan D. Dougherty
, Michael G. Katze
, Angela L. Rasmussen
, Sonja M. Best[SUP]6[/SUP][SUP],[/SUP]
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[SUP]5[/SUP]Co-first author
[SUP]6[/SUP]Lead Contact
[h=2]Highlights[/h]
[h=2]Summary[/h] The unprecedented 2013?2016 outbreak of Ebola virus (EBOV) resulted in over 11,300 human deaths. Host resistance to RNA viruses requires RIG-I-like receptor (RLR) signaling through the adaptor protein, mitochondrial antiviral signaling protein (MAVS), but the role of RLR-MAVS in orchestrating anti-EBOV responses in vivo is not known. Here we apply a systems approach to MAVS[SUP]−/−[/SUP] mice infected with either wild-type or mouse-adapted EBOV. MAVS controlled EBOV replication through the expression of IFNα, regulation of inflammatory responses in the spleen, and prevention of cell death in the liver, with macrophages implicated as a major cell type influencing host resistance. A dominant role for RLR signaling in macrophages was confirmed following conditional MAVS deletion in LysM+ myeloid cells. These findings reveal tissue-specific MAVS-dependent transcriptional pathways associated with resistance to EBOV, and they demonstrate that EBOV adaptation to cause disease in mice involves changes in two distinct events, RLR-MAVS antagonism and suppression of RLR-independent IFN-I responses.
full article
http://www.cell.com/cell-reports/fulltext/S2211-1247(16)31776-4
, Shelly J. Robertson[SUP]5[/SUP]
, Atsushi Okumura
, Dana P. Scott
, Jean Chang
, Jeffrey M. Weiss
, Gail L. Sturdevant
, Friederike Feldmann
, Elaine Haddock
, Abhilash I. Chiramel
, Sanket S. Ponia
, Jonathan D. Dougherty
, Michael G. Katze
, Angela L. Rasmussen
, Sonja M. Best[SUP]6[/SUP][SUP],[/SUP]
Press enter key to Email the author[SUP]5[/SUP]Co-first author
[SUP]6[/SUP]Lead Contact
[h=2]Highlights[/h]
- ? MAVS determines early differences in replication between WT and MA Ebola virus in mice
- ? MAVS controls expression of IFN-I, inflammatory responses, and cell death
- ? MAVS signaling specifically in myeloid cells is required for control of EBOV replication
- ? MAVS has both IFN-I-dependent and -independent roles in the control of EBOV
[h=2]Summary[/h] The unprecedented 2013?2016 outbreak of Ebola virus (EBOV) resulted in over 11,300 human deaths. Host resistance to RNA viruses requires RIG-I-like receptor (RLR) signaling through the adaptor protein, mitochondrial antiviral signaling protein (MAVS), but the role of RLR-MAVS in orchestrating anti-EBOV responses in vivo is not known. Here we apply a systems approach to MAVS[SUP]−/−[/SUP] mice infected with either wild-type or mouse-adapted EBOV. MAVS controlled EBOV replication through the expression of IFNα, regulation of inflammatory responses in the spleen, and prevention of cell death in the liver, with macrophages implicated as a major cell type influencing host resistance. A dominant role for RLR signaling in macrophages was confirmed following conditional MAVS deletion in LysM+ myeloid cells. These findings reveal tissue-specific MAVS-dependent transcriptional pathways associated with resistance to EBOV, and they demonstrate that EBOV adaptation to cause disease in mice involves changes in two distinct events, RLR-MAVS antagonism and suppression of RLR-independent IFN-I responses.
full article
http://www.cell.com/cell-reports/fulltext/S2211-1247(16)31776-4