Neurotropism of Theiler's murine encephalomyelitis virus

Theiler??s murine encephalomyelitis virus (TMEV) can infect the central nervous system (CNS) and cause neurological damage. The exact route by which TMEV enters the CNS remains unknown. Two hypotheses suggest that TMEV enters the CNS either by the neural and/or the hematogenous pathway. To explore these hypotheses, the GDVII strain of Theiler??s virus was inoculated via different routes in susceptible mice. The incidence of paralysis and/or encephalitis was evaluated. The forms of paralysis displayed corresponded to the site of viral inoculation. Following intramuscular (i.m.), intraperitoneal (i.p.), intravenous (i.v.) and footpad routes of injection, bilateral and or contralateral paralyses were observed. In mice injected intratongue, tongue paralysis was observed. Intracranial (i.c.) injections resulted in 100% mortality. A detailed time course experiment was also completed which focused on the neural transport pathway used by TMEV to invade the CNS. The GDVII strain of Theiler??s virus was injected into the left gastrocnemius muscle and the hypoglossal nerve (CN XII). The incidence of paralysis and/or encephalitis was evaluated on the basis of clinical signs, immunofluorescent analysis, and histopathology. Following the i.m., route of injection, unilateral hind limb paralysis was observed in the injected limb and a weakening of the contralateral limb was also observed. In mice injected in the hypoglossal nerve, tongue paralysis was observed. Also, the penis of most affected males was prolapsed. The localization of viral antigen using fluorescent labeling correlated with the clinical signs of paralysis for both injections. The studies reported here support the theory that GDVII Theiler??s virus may gain access to the CNS through a neural transport pathway.