Retrograde Transport of Intact Poliovirus Through the Axon via the Fast Transport System

Abstract

Intramuscularly inoculated poliovirus is thought to spread to the central nervous system through neural pathways in humans, monkeys, and the transgenic (Tg) mice carrying the human poliovirus receptor (PVR) gene. To gain insight into molecular mechanisms for the retrograde axonal transport of poliovirus, resulting in the expression of neurovirulence, a poliovirus-sensitive ICR-PVRTg21 mouse line (Tg21) was used as an animal model for poliomyelitis. We detected poliovirus antigens in axons of the sciatic nerve. All of the Tg21 mice, which had been inoculated into the calves with 1 x 10(6) pfu of the Mahoney strain of type 1 poliovirus, showed symptoms of paralysis in the inoculated limbs (initial paralysis) within 48 h after the inoculation. The appearance of this initial paralysis was observed in mice whose sciatic nerves were transected at various times after virus inoculation. The results were indicators of the velocity of poliovirus transportation through the sciatic nerves under analysis. Poliovirus-related materials recovered from the sciatic nerve were mainly composed of intact 160S virion particles. The amount of 160S particle recovered was greatly reduced by coinjection with anti-PVR monoclonal antibody. These results suggest that one of the fast retrograde axonal transport systems is involved in poliovirus dissemination through the sciatic nerve and that IM-inoculated poliovirus is incorporated into the sciatic nerve as intact particles in a PVR-dependent manner, as it is in humans.

Spectrum of disease outcomes in mice infected with YFV-17D

“…Previous studies have shown that neurotropic viruses can initiate infection in the periphery and can move through peripheral neurons to reach the central nervous system (Card et al, 1991;Ohka et al, 1998;Samuel et al, 2007;Tyler et al, 1986). Therefore, we hypothesized that mice with neurotropic disease may have higher viral titres in peripheral neurons and brain.…”

Receptor (CD155)-Dependent Endocytosis of Poliovirus and Retrograde Axonal Transport of the Endosome

“…PV is transported retrogradely by the fast axonal transport system, and PV antigen is detected inside axons (35). However, it is still unclear whether PV is enclosed in vesicles during its transport, although vesicles are known to be conveyed by the fast axonal transport system (6).…”

“…In that study, it was demonstrated that circulating PV after intravenous inoculation appears to cross the blood-brain barrier at a high rate, and the neural dissemination pathway from the skeletal muscle is not the primary dissemination route of the circulating virus to the central nervous system. Along with this pathway of dissemination, a neural pathway has been reported in humans (32), monkeys (20), and PV-sensitive transgenic (Tg) mice carrying the human PV receptor (hPVR/ CD155) gene (35,36), and it appears to be important in causing provocation poliomyelitis (14). Using the Tg mouse line, we demonstrate that PV inoculated into the calf is incorporated into the sciatic nerve and retrogradely transported through the axons as intact virion particles, that one of the fast retrograde axonal transport systems is involved in viral dissemination, and that the pathogenesis of PV infection via the neural pathway is inhibited by the anti-hPVR monoclonal antibody (MAb) p286, which is able to block the infection (35).…”

A nonpolio enterovirus with respiratory tropism causes poliomyelitis in intercellular adhesion molecule 1 transgenic mice

“…inoculation (24,25) or through viremia concomitant with skeletal muscle injury (16) is a known factor facilitating PV CNS invasion. Retrograde axonal transport of virus mediated by peripheral entry at the neuromuscular junction (NMJ) is suspected to account for this effect (16), because paralysis typically originates in the injected limb (the ''localization'' phenomenon; ref.…”