1. Injection of vesicular stomatitis virus into the leg muscles of young mice gives rise to flaccid paralysis of the inoculated extremity as the first clinical sign of a disease which is invariably fatal; old mice similarly injected with the largest doses of virus survive without exhibiting any signs of illness.
2. In young mice the virus was shown to multiply at the site of inoculation and to invade the sciatic nerve and spinal cord; there was no evidence of multiplication of virus in the blood or viscera.
3. In old mice, after intramuscular injection of as much as 10 million M.C.L.D., there was no evidence of either local or systemic multiplication; in spite of the persistence of thousands of M.C.L.D. of virus at the site of inoculation for at least 4 days, there was no detectable invasion of the sciatic nerve or the central nervous system.
4. Injection of the virus directly into the sciatic nerve of old mice led to the typical paralytic disease in half the number of animals.
5. For 3 days after intrasciatic injection the virus could be demonstrated in the nerve but not in the spinal cord or brain. At the onset of paralysis (6th day) virus was detectable in the spinal cord but no longer in the inoculated nerve.
6. The capacity of the virus to invade the central nervous system from the nerve but not from the muscle suggested the existence of a barrier in the muscle or myoneural junction.
7. Injection of the virus into the vitreous humor of the eye is followed by a fatal encephalitis in 15 day old mice, but 1 year old mice, with few exceptions, survive without showing signs of disease.
8. The spread of virus in the brains of intraocularly injected, 15 day old mice was too rapid to indicate the pathways which were pursued, but in 21 day old mice there was evidence that the primary pathway was probably along the axons of the optic nerve with decussation to the contralateral diencephalon and mesencephalon, and subsequent early spread to the corresponding occipital cortex. In resistant, old mice, however, no virus was found in any part of the brain.
Construction of Cationic Virosome Derived from Vesicular Stomatitis Virus as a Promising Candidate for Efficient Gene Delivery to the Central Nervous System
