Polio pathophysiology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: João André Alves Silva, M.D. [2]

Pathogenesis

Poliovirus enters the body through the mouth and infects nearby cells, such as those of the mouth, nose, and throat. The most common course of infection is the replication of poliovirus in cells of the gastrointestinal tract, followed by viral shedding in feces. The specific cells of the gastrointestinal tract, where poliovirus replicates, are not known, however, the virus was successfully isolated from lymphatic cells of the GI tract, including: tonsillar cells; Peyer's patches of the ileum, and lymph nodes of the mesenterium.

The virus enters the bloodstream, and migrates to reticuloendothelial cells across the body. Poliovirus is able to reach the central nervous system in a small fraction of the symptomatic patients. Not only isn't the disease a phase of the viral replication cycle, as it does not benefit poliovirus in any way. The molecular mechanisms behind the disease are not understood.

Poliovirus replicates inside primary monocytes, which allows it to spread from the initially infected cells, to the bloodstream. The pathogenesis behind the clinical manifestations of CNS infection by the virus results from the selective destruction of motor neurons. Motor neuron attack, may lead to symptoms such as paralysis, respiratory arrest and death. Although the mechanism of viral spread to the CNS is not fully understood, two theories persist:

1. Poliovirus diffuses directly through the blood brain barrier, from the bloodstream to the CNS, regardless of cellular receptors.
2. Poliovirus is transported from the muscle to the brain and spinal cord, through retrograde axonal transport. This hypothesis has been experimentally proven in mice, after CD155 transformation.

Retrograde Axonal Transport Hypothesis

Recent discoveries supporting the second hypothesis have been reported:

• Axonal presence of poliovirus, in patients with poliomyelitis, has been reported - This explains the "provocation poliomyelitis" phenomenon, in which muscle trauma, in the presence of viremia, was associated with an higher risk of developing poliomyelitis.
• In mice, genetically transformed to express CD155, after injection of poliovirus in the left limb, viral replication was noted only in the left anterior horn of the spinal cord, 33h after injection, before commencement of paralysis. When the sciatic nerve was promptly sectioned after injection of the virus, the predisposition of the implicated leg to be paralyzed was eliminated.
• In the same mice, if poliovirus was injected intravenously, poliomyelitis would manifest initially in the limb that had been injured by multiple empty needle injections. This leads to the idea that injured muscle opens a way for the virus to penetrate the terminal of the presynaptic motor neuron.
• Bulbar poliomyelitis following tonsillectomy may possibly be explained by the previously described mechanisms.
• There is over expression of CD155 on the muscle fibers of patients with paralytic poliomyelitis.
• CD155, directly interacts with the dynein retrograde complex, through Tctex-1.

In a synapse, the rate of endocytosis is related to the level of neuron activity. For the motor neuron, the level of neuron activity at the neuromuscular junction is associated with muscle contraction, therefore, increased muscle activity is related to increased rate of endocytosis. This explains the connection between extreme exercise activity and development of poliomyelitis in patients with viremia, since there is greater probability of viral uptake. Also, since most of CD155 receptors are transported back to the cell body, the virus is carried along, supporting the retrograde transport hypothesis.

Once at the cell body of the neuron, the change from axoplasm to cytoplasm is thought to interfere with the viral coat stability, leading to the exposure of the viral RNA. Viral replication interferes with neuron stability, killing the motor neuron. Death of the motor neuron paralyzes the respective muscle fiber. Spread of the virus to the nearby neurons will then be responsible for their death.

In the CNS, poliovirus shows tropism for certain pathways and tissues:

• Anterior horn cells of the spinal cord (in severe cases of the disease, the intermediate, intermediolateral and posterior gray columns may also be affected)
• Hypothalamus
• Thalamus
• Vestibular nuclei
• Deep cerebral nuclei
• Reticular formation
• Cerebellar vermis

Lesion distribution in paralytic and non-paralytic cases is the same. Additionally, inflammation can be detected in any affected area of the CNS, supporting the idea that in order to produce clinical manifestations, severe neuron damage must occur. The different clinical forms of poliomyelitis will depend on the most affected area of the CNS. Individual host factors and the neuropathogenicity of the virus influence the severity of the lesions.

Transmission

Poliovirus is transmitted through the fecal-oral route and through pharyngeal secretions.

Poliomyelitis is highly contagious and spreads easily from human-to-human contact. In endemic areas, wild polioviruses can infect virtually the entire human population. It is seasonal in temperate climates, with peak transmission occurring in summer and autumn. These seasonal differences are far less pronounced in tropical areas. The time between first exposure and first symptoms, known as the incubation period, is usually 6 to 20 days, with a maximum range of 3 to 35 days. Virus particles are excreted in the feces for several weeks following initial infection. The disease is transmitted primarily via the fecal-oral route, by ingesting contaminated food or water. It is occasionally transmitted via the oral-oral route, a mode especially visible in areas with good sanitation and hygiene. Polio is most infectious between 7–10 days before and 7–10 days after the appearance of symptoms, but transmission is possible as long as the virus remains in the saliva or feces.

Factors that increase the risk of polio infection or affect the severity of the disease include immune deficiency, malnutrition, tonsillectomy, physical activity immediately following the onset of paralysis, skeletal muscle injury due to injection of vaccines or therapeutic agents, and pregnancy. Although the virus can cross the placenta during pregnancy, the fetus does not appear to be affected by either maternal infection or polio vaccination. Maternal antibodies also cross the placenta, providing passive immunity that protects the infant from polio infection during the first few months of life.

Gallery

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  A photomicrograph of skeletal muscle tissue revealing myotonic dystrophic changes as a result of Polio Type III.Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.

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  A photomicrograph of the lumbar spinal cord depicting an infarct due to Polio Type III surrounding the anterior spinal artery.Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.

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  A photomicrograph of the lumbar spinal cord depicting an infarct due to Polio Type III surrounding the anterior spinal artery.Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.

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  A photomicrograph of the lumbar spinal cord depicting degenerative changes due to an infarct caused by Polio Type III.Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.

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  A photomicrograph of the thoracic spinal cord depicting degenerative changes due to Polio Type III.Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.

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  A photomicrograph of the thoracic spinal cord depicting degenerative changes due to Polio Type III.Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.

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  A photomicrograph of the cervical spinal cord in the region of the anterior horn revealing Polio Type III degenerative changes.Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.

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  A photomicrograph of the cervical spinal cord in the region of the anterior horn revealing Polio Type III degenerative changes.Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.

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  A photomicrograph of the cervical spinal cord in the region of the anterior horn revealing Polio Type III degenerative changes.Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.

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  Under a low magnification of 40X, this photomicrograph of a brain tissue specimen, specifically from the pontine region (pons), revealed histopathologic changes in a confirmed polio, or poliomyelitis patient. This tissue section was extracted from the pons at the level of the cranial nerve VI (CN VI) nucleus, which is also known as the abducens nerve.Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.

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  Photomicrograph of the Cervical Spinal Cord Affected by Polio Type III VirusAdapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.