Immunopathogenesis and immune modulation of Venezuelan equine encephalitisvirus-induced disease in the mouse

The course of Venezuelan equine encephalitis (VEE) disease in immunodeficie nt and immunologically normal mice was compared to define the role of the i mmune system in this disease process. Immunocompetent mice infected with VE E exhibited a biphasic illness characterized by an early self-limiting lymp hoid phase and a fatal CNS phase, The lymphoid phase of the illness was cha racterized by extensive viral replication within spleen, thymus, Peyer's pa tches, and lymph nodes, was accompanied by a high-titered serum viremia, an d resolved with the production of VEE-specific ISM class antibody at 72 h p ostinfection (p.i.). Immunocompetent animals survived an average of 6.8 +/- 1.2 days before succumbing to fulminant encephalitis. In contrast, SCID mi ce infected with VEE showed a persistent replication of virus throughout al l organs tested beginning at 24 h p,i. VEE-infected SCID mice exhibited a s evere spongiform encephalopathy with 100% mortality and an average survival time of 8.9 +/- 0.9 days. These studies indicated that the characteristic organ tropism of VEE in the mouse is due in large part to an early anti-vir al state, the establishment of which is dependent upon the presence of an i ntact immune system. Finally, the CNS pathology in a VEE-infected mouse had a significant immunologic component, However, in contrast to other neurovi rulent alphaviruses, VEE was directly cytopathic for the cells of the CNS, even in the absence of an immune response. (C) 2001 Academic Press.