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. 2012 Apr 18:3:147.
doi: 10.3389/fmicb.2012.00147. eCollection 2012.

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

Seii Ohka  1 , Coh-Ichi Nihei, Manabu Yamazaki, Akio Nomoto
Affiliations

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

Seii Ohka et al. Front Microbiol. .

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.

Keywords: axonal transport; blood–brain barrier; poliovirus; poliovirus receptor.

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Figures

FIGURE 1
FIGURE 1
Dissemination pathway for PV in human. Oral ingested PV invades into blood through alimentary tract (A) followed by viremia. The virus in the blood permeates BBB into CNS (B). PV also invades into CNS directly by neural pathway through MNs from skeletal muscle to CNS (C).
FIGURE 2
FIGURE 2
Mechanisms for hPVR-dependent and -independent transport of PV in MNs. (A) In hPVR-Tg mice, PV is endocytosed after interacting to hPVR (Aa). Most of the hPVR-containing vesicles are retrogradely transported in an hPVR-dependent manner with fast kinetics (Ac). hPVR-independent endocytosis (Ab) and transport (Ae) of PV also occur. The hPVR-independent endocytosis is possibly mediated by an unidentified PV receptor expressed at neuromuscular junctions. Alternatively, hPVR-independent endocytosis may be promoted by synaptic activity in vivo. PV-containing vesicles with or without hPVR can be retrogradely transported in an hPVR-independent manner with slow kinetics (Ad and Ae). (B) In non-Tg mice, PV is endocytosed and transported with slow kinetics in an hPVR-independent manner (Be). The hPVR-independent endocytosis is possibly mediated by the unidentified PV receptor expressed at neuromuscular junctions (Bb). (C) In cultured MNs, only hPVR-dependent PV endocytosis is detected (Ca).The hPVR-dependent transport shows fast kinetics (Cc). It might be possible that the slow component in cultured MNs (Cd) requires hPVR for endocytosis, whereas its transport may be hPVR-independent. (D) No endocytosis of PV is detected in cultured MNs lacking hPVR, possibly due to the absence of the unidentified PV receptor.
FIGURE 3
FIGURE 3
Models for BBB permeation of PV. TfR1 attaches to PV (A), transferrin (B), or PV peptide (C) and transported through brain capillary endothelial cells into brain by a fast process. On the other hand, dextran (MW > 15 K) is not transcytosed by TfR1 and leaks between cell junctions by a slow process (D).
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