Murine gammaherpesvirus-68 infection of and persistence in the central nervous system

Murine gammaherpesvirus-68 (MHV-68) was originally isolated from a bank vol e by passage through mouse brain. Given its ability to replicate in mouse b rain and its subsequent reisolation from trigeminal ganglia, it was origina lly considered to be an alphaherpesvirus, Molecular studies have now firmly established MHV-68 to be a gammaherpesvirus, Other gammaherpesviruses have been suggested to cause and in some cases shown to cause neurological dise ase, Given the isolation history of MHV-68, we have studied the ability of this virus to gain access to, to replicate in and to persist in the mouse C NS, Following intranasal inoculation the virus was not generally neuroinvas ive, However, in mice with a deletion of the type-I interferon receptor gen e, peripheral virus titres are higher and perivascular CNS infection was ob served, There was no evidence of virus spread via olfactory routes. Direct intracerebral inoculation of virus was fatal with widespread infection and destruction predominantly of meningeal and ependymal cells. Hippocampal pyr amidal neurons, oligodendrocytes, Bergmann glia cells in the cerebellar cor tex and neural progenitor cells in the rostral migratory stream were also i nfected. A similar infection was observed in younger mice. CNS infection fo llowing virus reactivation was investigated by implantation of infected gli al cells. Implantation into a brain ventricle led to widespread fatal infec tion, principally involving ependymal and meningeal cells. Implantation int o the striatum resulted in a predominantly neuronal infection. Implantation of cells into mice transiently treated with the antiviral thionucleoside a nalogue 2'-deoxy-5-ethyl-beta -4'-thiouridine resulted in survival with det ection of virus-infected cells in the brain 1 year later.