MURINE GAMMA-HERPESVIRUS-68 CAUSES SEVERE LARGE-VESSEL ARTERITIS IN MICE LACKING INTERFERON-GAMMA RESPONSIVENESS - A NEW MODEL FOR VIRUS-INDUCED VASCULAR-DISEASE

Fundamental issues remain unresolved regarding the possible contributi on of viruses to vascular pathology, as well as the role of the immune system in regulating these processes. Here we demonstrate that infect ion of mice with gamma-herpesvirus 68 (gamma HV68) provides a novel mo del for addressing these issues. Interferon-gamma receptor-deficient ( IFN gamma R-/-) mice died weeks to months after gamma HV68 infection f rom a severe large-vessel panarteritis. gamma HV68-infected B cell-def icient and normal weanling mice exhibited milder large-vessel arteriti s. Immunohistochemical analyses demonstrated gamma HV68 antigen in art eritic lesions and revealed a striking tropism of gamma HV68 for smoot h muscle cells. These studies demonstrate that IFN-gamma is essential for control of chronic vascular pathology induced by gamma HV68 and su ggest gamma-herpesviruses as candidate etiologic agents for human vasc ulitis.