| First Author | Dutta M | Year | 2017 |
| Journal | Cell Rep | Volume | 18 |
| Issue | 3 | Pages | 816-829 |
| PubMed ID | 28099857 | Mgi Jnum | J:254031 |
| Mgi Id | MGI:6103208 | Doi | 10.1016/j.celrep.2016.12.069 |
| Citation | Dutta M, et al. (2017) A Systems Approach Reveals MAVS Signaling in Myeloid Cells as Critical for Resistance to Ebola Virus in Murine Models of Infection. Cell Rep 18(3):816-829 |
| abstractText | 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(-/-) mice infected with either wild-type or mouse-adapted EBOV. MAVS controlled EBOV replication through the expression of IFNalpha, 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. |
