Chapter 21 : Poliomyelitis

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Poliovirus (PV) is the causative agent of poliomyelitis, an acute human disease of the central nervous system (CNS). This chapter provides a review of recent advances in our understanding of PV pathogenicity. The host range of most PV strains is restricted to primates, with humans as the natural host. The PV receptor (PVR) was identified by taking advantage of the species-specific nature of infection. Mouse cells are not susceptible to PV infection but permit PV replication when PV RNA is transfected, circumventing infection through the cell surface. The infected mice exhibit clinical signs and pathological lesions that resemble human poliomyelitis after intracerebral, intraperitoneal, intravenous, intramuscular, or intranasal inoculation of PV. In addition to monkeys, PVR-Tg21 mice are recognized by the World Health Organization as an animal model of poliomyelitis. Provocation poliomyelitis was experimentally reproduced in transgenic (tg) mice, with results that suggested that skeletal muscle injury stimulates retrograde axonal transport of PV and thereby facilitates viral invasion of the CNS, with resultant spinal cord damage. The quasispecies of PV plays an important role in PV pathogenesis. PV, as well as other RNA viruses, has a high error rate in RNA replication, and therefore each viral genome in the population differs from others by one or more mutations.

Citation: Koike S, Nomoto A. 2010. Poliomyelitis, p 339-351. In Ehrenfeld E, Domingo E, Roos R (ed), The Picornaviruses. ASM Press, Washington, DC. doi: 10.1128/9781555816698.ch21
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Image of Figure 1.
Figure 1.

Scheme of PV pathogenesis and possible barriers that prevent PV dissemination. There are several host barriers that block the progression of PV dissemination. The host range of PV is restricted to simians, so other animal species are not susceptible to PV infection (host range barrier). In humans, after PV is ingested, PV initially replicates in the oropharyngeal and intestinal mucosa and enters the host despite a physical barrier at the GI mucosa (GI tract barriers). When PV reaches the blood, PV replicates poorly in the extraneural tissues, suggesting the presence of a barrier that prevents efficient replication of PV in these tissues. The CNS is physically isolated from the extraneural tissues by the blood-brain barrier (BBB), which acts as a physical barrier preventing free movement of substances between the bloodstream and the parenchyma of the CNS. PV permeates this barrier by an unknown mechanism. PV also reaches the CNS via retrograde axonal transport, a pathway for PV that is dependent on the PVR. PV finally replicates in neurons in the CNS. The replication sites in the CNS are restricted to certain neurons, suggesting the presence of unknown barriers in nonsusceptible neurons. Replication of attenuated PV strains is strongly suppressed in neurons, suggesting PV strain-specific barriers in the CNS.

Citation: Koike S, Nomoto A. 2010. Poliomyelitis, p 339-351. In Ehrenfeld E, Domingo E, Roos R (ed), The Picornaviruses. ASM Press, Washington, DC. doi: 10.1128/9781555816698.ch21
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Image of Figure 2.
Figure 2.

Structure of the GI tract barrier. The epithelial cells (enterocytes) lining the GI tract form a tight physical barrier for PV infection. A structure called FAE is present in Peyer’s patches above the lymphoid follicle and contains M cells, which are capable of transporting molecules from the intestinal lumen into the underlying dendritic cells or macrophages. The primary replication sites of PV and the source of excreted virus have not yet been determined. It is also unknown whether PV replicates in the epithelial cells in a PVR-dependent manner or whether PV is incorporated via M cells by transcytosis without lytic infection.

Citation: Koike S, Nomoto A. 2010. Poliomyelitis, p 339-351. In Ehrenfeld E, Domingo E, Roos R (ed), The Picornaviruses. ASM Press, Washington, DC. doi: 10.1128/9781555816698.ch21
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Image of Figure 3.
Figure 3.

Innate immune barrier in extraneural tissues. Although many tissues are exposed to PV during the viremic phase, PV replication in the extraneural tissues is strongly suppressed by the innate immune response, which is mediated by type I IFN. Many cells in the extraneural tissues possess all of the host factors required for PV replication and have the potential to support PV replication. Soon after infection of a single cell, an active host innate immune defense induces an antiviral state in the surrounding cells and stops the cascade of viral infection in these sites. Thus, this response acts as an immunological barrier. In neural tissues, however, the innate immune response is less active than in the extraneural tissues, allowing a sequential cascade of viral infection.

Citation: Koike S, Nomoto A. 2010. Poliomyelitis, p 339-351. In Ehrenfeld E, Domingo E, Roos R (ed), The Picornaviruses. ASM Press, Washington, DC. doi: 10.1128/9781555816698.ch21
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Image of Figure 4.
Figure 4.

Two pathways of CNS invasion. PV is able to enter the CNS by at least two distinct pathways. One pathway involves the direct penetration of the BBB from the bloodstream into the parenchyma of the CNS. The BBB is composed of endothelial cells of blood vessels that are sealed together at their edges by tight junctions. Generally, it does not allow free transport of pathogens. There is no strong evidence that supports direct infection of endothelial cells. Physiological pharmacokinetic analysis suggests that the PV is able to permeate the BBB from the bloodstream into the parenchyma of the CNS independently of PVR. The precise mechanism by which PV employs this pathway remains to be elucidated. Another pathway leading to neural dissemination of PV is by retrograde axonal transport. PV is incorporated into endosomes by PVR-mediated endocytosis at neuromuscular junctions. The C-terminal cytoplasmic tail of the PVR on the surface of the endosome is able to bind TCTEL1 (in humans) or Tctex-1(in mice), which is the light chain-1 of the cytoplasmic dynein complex. PV-containing endosomes move on the microtubules along the axon via retrograde transport at a rate of more than 12 cm/day, a velocity classified as fast retrograde axonal transport. PV particles do not initiate conformational changes during transport along the axon until they reach the cell body of the neuron.

Citation: Koike S, Nomoto A. 2010. Poliomyelitis, p 339-351. In Ehrenfeld E, Domingo E, Roos R (ed), The Picornaviruses. ASM Press, Washington, DC. doi: 10.1128/9781555816698.ch21
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