A Systems Approach Reveals MAVS Signaling in Myeloid Cells as Critical for Resistance to Ebola Virus in Murine Models of Infection

Mukta Dutta5
, Shelly J. Robertson5
, 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. Best6,Press enter key for correspondence informationPress enter key to Email the author
5Co-first author
6Lead Contact

  • 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


The unprecedented 20132016 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 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.

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