Figure 7

Proposed model by which glia recognize neurotropic DNA viruses such as HSV-1 and elicit inflammatory CNS damage. Replicating DNA viruses generate genomic DNA that serves as a ligand for DAI. DAI then associates with IPS-1 and STING, subsequently activating NF-kB via the actions of RIP1 and RIP3. In addition, it is possible that RNA polymerase III (Pol III) in the cytosol could transcribe viral DNA into dsRNA containing 5'-triphosphate (ppp-dsRNA), that could be recognized by RIG-I and similarly activate NF-kB via IPS-1 and STING. Activated NF-kB subunits then translocate to the nucleus and initiate the production of inflammatory mediators. These soluble mediators could then promote inflammation, increase blood-brain-barrier permeability, recruit leukocytes into the CNS, and directly or indirectly initiate neuronal cell damage and/or death.