Variations in Pathways by Which Equine Encephalomyelitic Viruses Invade the GNS of Mice and Guinea-pigs

Abstract

Eastern equine encephalomyelitic (E.E.E.) virus, injected into the leg muscles of 15- to 21-day-old mice, invades the central nervous system (CNS) along the local peripheral nerves in only about 5% of the animals, while in most of the others it appears to be eliminated from the blood onto the olfactory mucosa, invading the CNS by the olfactory pathway, and when that pathway is blocked by preliminary chemical treatment of the nasal mucosa most, but not all, of the animals escape CNS involvement. 1 Further study by the method of partial serial sections of the entire CNS 2 revealed that when mice, given the virus intranasally, succumb in spite of the chemical treatment, the lesions are still distributed along the olfactory pathways and connections, showing that the treatment did not provide a complete barrier. When, however, mice receiving the virus intramuscularly succumb in spite of chemical blockade of the olfactory pathway, the localization of lesions indicates that the CNS was invaded by other pathways, the following types having been encountered: (a) lesions limited to the spinal cord and medulla, indicative of spread via the nerves supplying the inoculated muscle; (b) lesions involving chiefly the cochlear ganglion of one side and the inferior colliculus and medial geniculate body of the opposite side (i.e., a unilateral involvement of the auditory pathway and its central connections); and (c) lesions limited to a focus in the vicinity of the medullary nucleus of the 7th nerve. Hence, these and other pathways may occasionally be utilized by virus injected into the leg muscles (and also intraäbdominally) of normal mice as well as of those with chemical blockade of the olfactory pathway. In one normal young mouse injected intraäbdominally with E.E.E. virus both the auditory and vestibular pathways appeared to be involved. It is remarkable, however, that in these mice the localization of lesions practically always corresponded to some definite pathway, suggesting that the virus was set free in one focus from which it spread along the nervous pathways connected with it (excepting the olfactory pathway, there is as yet no evidence to indicate whether that focus is within or outside the CNS) rather than liberated indiscriminately throughout the CNS.