Murine γ-herpesvirus 68 causes severe large-vessel arteritis in mice lacking interferon-γ responsiveness:: A new model for virus-induced vascular disease

Fundamental issues remain unresolved regarding the possible contribution of viruses to vascular pathology, as well as the role of the immune system in regulating these processes. Here we demonstrate that infection of mice with gamma-herpesvirus 68 (gamma HV68) provides a novel model for addressing these issues. Interferon-gamma receptor-deficient (IFN gamma R-/-) mice died weeks to months after gamma HV68 infection from a severe large-vessel panarteritis. gamma HV68-infected B cell-deficient and normal weanling mice exhibited milder large-vessel arteritis. Immunohistochemical analyses demonstrated gamma HV68 antigen in arteritic lesions and revealed a striking tropism of gamma HV68 for smooth muscle cells. These studies demonstrate that IFN-gamma is essential for control of chronic vascular pathology induced by gamma HV68 and suggest gamma-herpesviruses as candidate etiologic agents for human vasculitis.