Background Paper On the Role of the Immune Response in the Course of Coronavirus JHM-Induced Encephalomyelitides in Mice and Rats

Virus infections of the central nervous system (CNS) may result in the loss of myelin sheaths without axonal destruction. Severe neurological symptoms occur as a consequence of this phenomenon which is called primary demyelination. The sequence of events leading to primary demyelination during the course of viral infections of the CNS is only partially understood. Although it is well established that cytolytic infection of the Oligodendroglia cell can cause primary demyelination, mononuclear infiltrates in subacute and chronic courses of the disease indicate that immunological events may take part in this process (reviewed by Johnson (1)). For several reasons, investigations into the dynamic interactions between virus infection of the CNS and the local immune response cannot be conducted in man. (1) Usually clinical specimens are restricted to cerebrospinal fluid which gives limited information about pathological events occuring in the brain parenchyma (2). It is not known at which time point of the preceeding systemic infection, the virus enters the brain and biopsies are taken too rarely and infrequently to understand the kinetics of the events (3). The general absence of genetic homogeneity in man complicates attempts to detect the influence of the immunogenetic background on the course of the disease. In contrast, intracerebral infections of rodents with the murine hepatitis virus JHM (MHV-4) are excellent models to study the relationships between virus-induced demyelination and the local immune response. Based on the work of Cheever (2), animal models of JHM virus-induced demyelinating encephalomyelitis have been developed in mice as well as in rats (3–5). In recent years striking similarities in the course of the infection in both rodents have been detected which might give the impression that these two models can substitute for each other. However, subtle but important differences do exist. Therefore, in the present review attempts are made to summarize and compare the knowledge about demyelinating encephalomyelitides in rats and mice, giving emphasis to the role of the local immune response in the brain.