Mechanisms of virus-induced neuronal damage and the clearance of viruses from the CNS.

Abstract

The pathogenic mechanisms underlying virus-induced neurological disease are complex but fall into two general categories, neuronal damage or dysfunction, resulting: (1) from within, as a direct consequence of the virus infection, and (2) from without, due to the indirect action of resident and invading immune/inflammatory cells responding to viral antigens. Our studies have focused on two viruses that can cause acute, lethal neurological diseases representative of these classes: rabies virus (RV) and Borna disease virus (BDV). RV infection induces significant electrophysiological changes in the CNS and sleep alterations but is accompanied by only minor histopathological changes in the CNS (Gourmelon et al. 1986, 1991). In contrast, acute Borna disease is associated with extensive neuropathology including astrogliosis, perivascular cuffing, monocytic infiltration of the brain parenchyma, and massive neuronal loss (Right et al. 1990; Gosztonyi and Ludwig 1995; Stitz et al. 1995; Morimoto et al. 1996), which are dependent on a BDV-specific immune response. The profound difference in the pathogenesis of rabies and Borna disease is evidenced by the fact that immunosuppression either has no effect or is detrimental to the outcome of rabies infection but is therapeutic in Borna disease (Stitz et al. 1995; Morimoto et al. 1996). Despite the clear differences in neuropathology between rabies and Borna disease, there are immune strategies for each that can evidently clear these viruses from the CNS thereby preventing a lethal outcome to the infections (Dietzschold et al. 1992; Dietzschold 1993; Richt 1994). Further knowledge of the different pathogenic processes underlying rabies and Borna disease is key to the development of therapeutic strategies for diverse CNS viral diseases. In this chapter we discuss the response of CNS resident cells to infection, the link between these responses and the induction of virus-specific immunity, and the mechanisms through which virus can be cleared from the CNS.KeywordsRabies VirusInfected NeuronRabies Virus InfectionRabies Virus StrainSleep AlterationThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.