The STING agonist 5,6-dimethylxanthenone-4-acetic acid (DMXAA) stimulates an antiviral state and protects mice against herpes simplex virus-induced neurological disease.

Herpes simplex virus (HSV)- 1 is the most common cause of sporadic viral encephalitis and accounts for 5-10% of cases worldwide. A key factor in host control of viral infection is the initiation of the interferon (IFN) response, mediated in part by the stimulator of interferon genes (STING) pathway. In these studies, we examined the ability of 5,6-dimethylxanthenone-4-acetic acid (DMXAA), a STING agonist, to protect against HSV-1 infection. DMXAA reduced viral replication through increased production of type I IFN in vitro. Furthermore, administration of DMXAA to HSV-1 infected mice resulted in a reduction of viral burden in the peripheral and central nervous systems. This reduced viral burden also correlated with increased survival of DMXAA-treated infected mice. These results therefore demonstrate the potential of STING agonists for immunotherapy against HSV-1.