Molecular Basis of Neuropathogenicity of Mouse Hepatitis Virus

Abstract

The JHM strain of mouse hepatitis virus (MHV), a member of the Coronaviridae, was one of the earliest recognized neurotropic viruses. It was isolated from a paralytic mouse by F. S. Cheever et al. in 1949 (1, 2), and subsequently shown to cause encephalitis and demyelinating lesions upon intracerebral injection into mice (1, 3, 4, 5). The virus has a predilection for oligodendrocytes, causing primary demyelination with axonal sparing (3). The neuropathogenic properties of the virus in mice vary with the genetic background of the mouse strains and appear to be controlled by one or more host genes (6, 7, 8). Furthermore, several different strains of MHV have been isolated that differ markedly in their neuropathogenic properties. Thus, this system offers an experimental model in which both the host and viral genes influencing neuropathogenesis can be examined. Coronavimses, particularly MHV, also exhibit several unique features of virion structure and replication strategy (9), which make the MHV model a particularly interesting system. This chapter will emphasize the role of viral genes and the molecular approaches to the problems of MHV neuropathogenesis. A recent review has examined the role of host responses in this system (10).