Involvement of Microtubules and the Microtubule-Associated Protein TAU in Trafficking of JHM Virus and Components within Neurons

The neurotropic coronavirus JHM (JHMV) is capable of inducing various forms of CNS disease in rodents, ranging from an acute encephalomyelitis to a delayed onset demyelination1,2,3. In rats, during the early stages of the disease process, neurons become cellular targets3,4. When introduced by intranasal inoculation, JHMV can invade the CNS of mice and rats by spreading along the olfactory neurons5,6,7,8. Virus spread was shown to occur by the transneuronal route5,8. Subsequent spread within the CNS seems to involve specific neuronal populations and tracts6,8. In particular, in Wistar Furth rats, Purkinje and hippocampal neurons are extensively involved3,4. Moreover, neurons have been shown to provide a repository site where both RNA and virions can persist for prolonged periods9,10, 11. Recently, Pasick et al., (1994) demonstrated that trafficking of virus materials within neurons occurs asymmetrically along somatodendritic and axonal processes, and appears to be dependent on the integrity of the microtubular network, as evident from analyses by light and electron microscopy which revealed that JHMV nucleocapsids (N) are closely associated with microtubules12, 13. This report seeks to define, more directly, by immunoprecipitation and immunoblotting, interactions between N and the microtubular arrays.