Neuroinvasive Vesicular Stomatitis Virus (VSV) rapidly activates multiple cytokine genes in the olfactory bulb and hippocampus. Controllable and uncontrollable stress (modeled by escapable and inescapable shock (ES and IS), respectively) amplify cytokine gene expression by augmenting type I interferon (IFN-I) and Rig-I (retinoic acid-inducible gene I) signaling through a mir146a-dependent pathway. Ingenuity Platform Analysis identified shared network nodes including IRF7, TLRs and RIG-I. ES uniquely included TLR/MYD88 and CD80 activation while IS activated several cytokines, CD40 and OAS2. Thus, stressor controllability differentially regulates neuroimmune responses to VSV with likely mediation by stress-responsive miR146a and its influence on different proinflammatory mediators.