Imagine conquering a potentially life-threatening disease like poliomyelitis—only to have joint pain, decreased endurance, and atrophied muscles 30 years later. Imagine, too, doctors dismissing your problems as existing only in your mind, because modern medical literature contains little about delayed changes in the nervous system of polio survivors. Today, doctors recognize postpolio syndrome (PPS)—the residual weakness patients who have survived a bout with polio can experience decades after the initial acute infection—as a legitimate clinical condition. But researchers are still struggling to understand its causes.

How the virus infects a cell

To understand PPS, it is first necessary to understand how poliovirus infects a cell. The ability of the poliovirus to attack certain cells, such as neurons, depends on the presence of a cell membrane receptor specific to poliovirus. After binding to the receptor, the virus penetrates the cell and releases its genetic material, which consists of a single strand of RNA that codes for the viral proteins.

The outer shell of poliovirus resembles an icosahedral structure with 60 identical repeating subunits (protomers). Each protomer is made up of four protein-like chains. The shell encloses a core of a single-stranded RNA molecule about 7,500 nucleotides long.

The virus seizes the host cell's machinery in order to translate its own RNA into proteins, shutting off host protein synthesis. A single very large protein is produced that is then sliced up into roughly a half dozen functional proteins and four structural ones.

How the virus manages to shut off protein synthesis in the host cells has intrigued investigators. A key action appears to be the inactivation of a special protein, translation initiation factor eIF-4F, that the host cell uses to start synthesizing the proteins it needs.

How the virus produces paralysis

The virus probably enters the central nervous system (the spinal cord and brain) either by traveling along peripheral nerves or via the circulatory system by penetrating the blood-brain barrier. The attraction the virus shows for nerve cells that control muscles is a distinctive characteristic of acute poliovirus infection. Poliovirus infects and destroys motor neurons, leaving virtually untouched adjacent nerve cells that control sensation, bowel movement, bladder function, and even sexual arousal. The receptors on the nerve cells allow the virus to enter an axon and then to migrate into the spinal cord or the virus may enter the nervous system via the bloodstream. The virus infects motor neurons in the spinal cord and cells in the brain. The infected cells die, and if enough neurons attached to a muscle die, muscle weakness or paralysis results.

How infection may lead to postpolio syndrome

A growing consensus among researchers suggests that PPS involves a slow degeneration of the ends of the motor neurons projections that contact and stimulate muscles.

Why these projections degenerate remains a mystery. The most plausible hypothesis is that muscles weakened by polio have to work harder just to maintain daily activities, causing the motor neurons to be overworked and to "wear out" faster. Evidence also suggests that some of the motor nerve cells are damaged during the acute infection and are then more vulnerable to failure over time.

The persistence of the body of poliovirus particles that have lain dormant for many years and then are then reactivated by some unknown mechanism may also play a role. Researchers have reported poliovirus-like RNA fragments in the spinal fluid and spinal cord tissue of some patients with PPS, but not in polio survivors without the syndrome. These small fragments do not, however, appear to be infectious. Other possible causes of PPS include immune-mediated response, hormone deficiencies, and environmental poisons, although evidence in support of any of these causes is not strong.

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