Poliovirus trafficking toward central nervous system via human poliovirus receptor-dependent and -independent pathway.

Seii Ohka,Manabu Yamazaki,Akio Nomoto,Coh-Ichi Nihei

doi:10.3389/fmicb.2012.00147

Abstract

In humans, paralytic poliomyelitis results from the invasion of the central nervous system (CNS) by circulating poliovirus (PV) via the blood–brain barrier (BBB). After the virus enters the CNS, it replicates in neurons, especially in motor neurons, inducing the cell death that causes paralytic poliomyelitis. Along with this route of dissemination, neural pathway has been reported in humans, monkeys, and PV-sensitive human PV receptor (hPVR/CD155)-transgenic (Tg) mice. We demonstrated that a fast retrograde axonal transport process is required for PV dissemination through the sciatic nerve of hPVR-Tg mice and that intramuscularly inoculated PV causes paralysis in a hPVR-dependent manner. We also showed that hPVR-independent axonal transport of PV exists in hPVR-Tg and non-Tg mice, indicating that several different pathways for PV axonal transport exist in these mice. Circulating PV after intravenous inoculation in mice cross the BBB at a high rate in a hPVR-independent manner. We will implicate an involvement of a new possible receptor for PV to permeate the BBB based on our recent findings.

Highlights

Poliovirus (PV), known to be the causative agent of poliomyelitis, is a human enterovirus that belongs to the Picornaviridae
We demonstrated that a fast retrograde axonal transport process is required for PV dissemination through the sciatic nerve of hPVR-Tg mice and that intramuscularly inoculated PV causes paralytic disease in a hPVR-dependent manner (Ohka et al, 1998)
We showed that hPVR-independent axonal transport of PV exists in hPVR-Tg and non-Tg mice, indicating that several different pathways for PV axonal transport exist in these mice (Ohka et al, 2009)

Summary

INTRODUCTION

Poliovirus (PV), known to be the causative agent of poliomyelitis, is a human enterovirus that belongs to the Picornaviridae. The two dissemination routes through BBB and MNs are functional in PV-sensitive Tg mice, whereas the routes through alimentary mucosa is not functional in PV-sensitive Tg mice with normal IFN-α/β response. PVR-DEPENDENT AND -INDEPENDENT RETROGRADE AXONAL TRANSPORT FROM MUSCLE TO CNS Axonal transport is a cellular process responsible for movement of mitochondria, lipids, synaptic vesicles, proteins, and organelles to and from a neuron’s cell body, through the cytoplasm of its axon. It is well known that some viruses, such as Rabies virus, hijacks the retrograde axonal transport, i.e., from synapse to cell body, to invade the CNS (Warrell and Warrell, 2004). We demonstrated that a fast retrograde axonal transport process is required for PV dissemination through the sciatic nerve of hPVR-Tg mice and that intramuscularly inoculated PV causes paralytic disease in a hPVR-dependent manner (Ohka et al, 1998).

Poliovirus trafficking toward CNS

Findings

CONCLUSION