MAVS mediates a protective immune response in the brain to Rift Valley fever virus

Rift Valley fever virus causes severe disease in humans and livestock and in some cases can be fatal. There is concern about the use of Rift Valley fever virus as a bioweapon since it can be transmitted through the air, and there are no vaccines or antiviral treatments. Airborne transmission of the virus causes severe inflammation of the brain, yet little is known about the immune response against the virus in this organ. Here, we investigated the immune response in the brain to Rift Valley fever virus following intranasal infection. We determined that microglia, the resident immune cells of the brain, initiate a robust response to Rift Valley fever virus infection and identified a key immune pathway that is critical for the ability of microglia to respond to infection. When this immune pathway is rendered non-functional, mice have a dysregulated response to infection in the brain. C57BL/6J or Mavs-/- male and female mice (12 weeks old) were inoculated intranasally with 5x10^5 PFU RVFV MP-12. Brains were isolated from infected and uninfected control animals on day 7 post-infection. A single cell suspension was generated from whole brain and cells were sequenced to obtain single-cell level gene expression profiles.