Efficient Delivery of Circulating Poliovirus to the Central Nervous System Independently of Poliovirus Receptor

AbstractThe transgenic (Tg) mice carrying the human gene for poliovirus receptor (PVR) are susceptible to poliovirus intravenously (IV) inoculated as well as intracerebrally or intraspinally inoculated. Thus, IV-inoculated poliovirus may invade the central nervous system (CNS) through the blood–brain barrier (BBB). To know the contribution of PVR to tissue distribution and BBB permeability of IV-inoculated polioviruses, these dissemination processes were investigated and compared between the Tg mice and non-Tg mice. Distribution profile of IV-inoculated poliovirus in various tissues of the Tg mice is similar to that in non-Tg mice. The data suggest that tissue distribution of the virus occurs independently of the transgene for PVR. The amount of poliovirus delivered to the CNS suggested the existence of a specific delivery system of the virus to the CNS. Virus accumulation in the CNS of the Tg mice was measured up to 7.5 hr after the IV inoculation. The viruses, regardless of whether the virulent or attenuated strain, seem to accumulate at a constant rate of approximately 0.2 μl/min/g tissue. Similar phenomena were observed when the viruses were inoculated into non-Tg mice. The rates of the virus accumulation in the CNS are more than 100 times higher than that of albumin, which is considered not to permeate through the BBB via a specific transport system, and only three times lower than that of monoclonal antibody against transferrin receptor (OX-26), which is a potential candidate as a drug delivery vehicle specific to the CNS. These data suggest that polioviruses permeate through the BBB at a fairly high rate, independently of PVR and virus strains