Ongoing viral replication is required for gammaherpesvirus 68-induced vascular damage

The role of autoimmunity in large-vessel vasculitis in humans remains uncle ar. We have previously shown that infection of gamma interferon receptor kn ockout (IFN-gammaR(-/-)) mice with gammaherpesvirus 68 (gamma HV68) results in severe inflammation of the large elastic arteries that is pathologicall y similar to the lesions observed in Takayasu's arteritis, the nongranuloma tous variant of temporal arteritis, and Kawasaki's disease (K. E. Week et a l., Nat. Med. 3:1346-1353, 1997). Here we define the mechanism of damage to the elastic arteries. We show that there is a persistent productive infect ion of the media of the large elastic vessels. In addition, we demonstrate that persistent virus replication is necessary for chronic arteritis, since antiviral therapy of mice with established disease resulted in increased s urvival, clearance of viral antigen from the media of the affected vessel, and dramatic amelioration of arteritic lesions. These data argue that ongoi ng virus replication, rather than autoimmunity, is the cause of gamma HV68- induced elastic arteritis.