Polio Virus- An Overview

Polio virus is a member of the family of picornavirus, which are small, non-enveloped viruses with a single-stranded positive-sense RNA genome.

The genome of polio virus is a single-stranded positive-sense RNA molecule that is about 7.5 kilobases long. It encodes a single large polyprotein that is cleaved by viral and cellular proteases into 11 functional proteins. The genome has three main regions: a 5′ noncoding region (NCR), an open reading frame (ORF), and a 3′ NCR.

• Polio virus infection was once a global public health problem, causing epidemics of paralysis and death in many countries.
• The disease mainly affects children under 5 years of age, who are more susceptible to infection and severe complications.
• Polio virus is transmitted by person-to-person contact, mainly through the fecal-oral route or contaminated water or food sources.
• The virus can be shed in the throat and stools of infected individuals for several weeks, even if they have no symptoms or mild illness.
• The virus can also spread to the central nervous system and cause irreversible damage to the motor neurons, resulting in flaccid paralysis or respiratory failure.
• There are three serotypes of polio virus (type 1, type 2 and type 3), each requiring a specific immune response to confer protection.
• Since the launch of the Global Polio Eradication Initiative (GPEI) in 1988, the incidence of polio worldwide has been reduced by 99%, from an estimated 350 000 cases in more than 125 endemic countries then, to 6 reported cases in 2021.
• The introduction of effective vaccines (inactivated polio vaccine, IPV and oral polio vaccine, OPV) has been the main strategy to prevent and eliminate polio.
• However, as long as a single child remains infected, there is a risk of polio resurgence and re-infection of polio-free areas.
• Therefore, high vaccination coverage, sensitive surveillance and rapid response to outbreaks are essential to achieve and maintain a polio-free world.

Polio virus replicates in the cytoplasm of the infected cells, using its own enzymes and host cell machinery. The replication cycle can be divided into several steps:

• Attachment and entry: The virus binds to a cellular receptor called CD155, which is present on the surface of many cell types, such as neurons, epithelial cells, and immune cells. The binding triggers a conformational change in the viral capsid, which allows the virus to form a pore in the cell membrane and release its RNA genome into the cytoplasm.
• Translation: The viral RNA is uncapped and has a protein called VPg attached to its 5` end. It also has a long non-coding region (NCR) at both ends, which contains an internal ribosome entry site (IRES). The IRES mediates the translation of the viral RNA by internal ribosome binding, without the need for a cap structure. The viral RNA is translated into a single polyprotein, which is then cleaved by viral and host proteases into several structural and non-structural proteins.
• RNA synthesis: The viral RNA forms a complex with viral proteins VPg and 3D (RNA-dependent RNA polymerase) and host proteins on membrane vesicles derived from the endoplasmic reticulum. The complex initiates the synthesis of a negative-strand RNA from the positive-strand RNA template. The negative-strand RNA then serves as a template for the synthesis of multiple positive-strand RNAs, which can be used for translation or packaging. The viral RNA synthesis requires the circularization of the genome through a long-range interaction between the 5` and 3` NCRs mediated by viral and host proteins.
• Assembly and release: The newly synthesized positive-strand RNAs interact with the structural proteins VP0, VP1, VP3, and VP4, which form pentameric subunits called protomers. Five protomers assemble into an icosahedral capsid called procapsid, which contains 60 copies of each structural protein. The procapsid undergoes a maturation process, in which VP0 is cleaved into VP2 and VP4, and VP4 is partially externalized. The maturation increases the stability and infectivity of the virion. The mature virions are released from the cell by lysis or exocytosis.

The pathogenesis of polio virus involves the following steps:

• The mouth is the portal of entry for the virus, transmitted by fecal-oral route on ingestion of contaminated water or food.
• The virus initially multiplies in the oropharynx and gastrointestinal mucosa, where it can be detected in the throat and in the stools before the onset of illness.
• The virus then spreads to regional lymph nodes and enters the blood, causing primary viremia. Antibodies to the virus appear early in the disease, usually before paralysis occurs. The antibodies can prevent further infection from spreading.
• During the period of viremia, the polio virus crosses the blood-brain barrier and gains access to the central nervous system (CNS), where it shows tissue tropism by specifically infecting neural cells.
• The virus recognizes and binds to a cellular receptor present on the anterior horn of spinal cord, dorsal root ganglia, and motor neurons. The receptor is a glycoprotein called CD155 or poliovirus receptor (PVR).
• The virus enters the cell by endocytosis and uncoats its RNA genome, which is then translated and replicated by the viral enzymes and host cell machinery.
• The viral replication causes damage and destruction of motor neurons, leading to paralysis of the muscles innervated by them. The paralysis can be asymmetric, affecting one or more limbs, or symmetric, affecting both sides of the body. The paralysis can also affect the muscles of respiration, swallowing, and speech, causing respiratory failure, dysphagia, and dysarthria.
• The virus can also infect the brain stem, causing bulbar poliomyelitis. This condition affects the cranial nerves, most commonly 9th (glossopharyngeal), 10th (vagus), and 12th (hypoglossal). This can result in difficulty in breathing, swallowing, speaking, and controlling heart rate and blood pressure. Bulbar poliomyelitis is often fatal.
• The extent and severity of paralysis depend on several factors, such as the strain and dose of virus, the age and immune status of the host, and the time of onset of symptoms. Most cases of poliomyelitis are asymptomatic or mild, but about 1% of infections result in paralytic poliomyelitis. The mortality rate is variable and is highest in older patients. It may range from 5% to 10%.

Polio virus infection can cause a range of symptoms, depending on the extent of viral invasion and damage to the nervous system. The symptoms can be classified into four categories: asymptomatic, abortive, non-paralytic, and paralytic.

• Asymptomatic infection occurs when the virus is confined to the oropharynx and the intestine, without causing any visible signs or symptoms. This is the most common outcome of polio virus infection, affecting about 95% of infected people.
• Abortive poliomyelitis is a minor illness that occurs in about 5% of infected people. It is characterized by flu-like symptoms such as fever, headache, sore throat, loss of appetite, vomiting, and abdominal pain. These symptoms usually last 2 to 5 days and then resolve spontaneously. Neurological symptoms are typically absent in this category.
• Non-paralytic poliomyelitis affects some people who develop symptoms from the polio virus but do not experience paralysis. This category accounts for about 1–5% of infected people. The symptoms include fever, headache, sore throat, vomiting, fatigue, back pain or stiffness, neck pain or stiffness, pain or stiffness in the arms or legs, and muscle weakness or tenderness. These symptoms can last up to 10 days.
• Paralytic poliomyelitis is the most severe and rare outcome of polio virus infection, affecting about 0.05–1% of infected people. It occurs when the virus invades the spinal cord or brain stem and destroys the motor neurons that control muscle movement. The paralysis can affect one or more limbs, or the muscles involved in breathing or swallowing. The symptoms include loss of reflexes, severe muscle aches or weakness, loose and floppy limbs (flaccid paralysis), difficulty breathing or swallowing, and sometimes death. Paralysis usually develops within a week after the onset of fever and headache. Paralysis can be permanent or temporary, depending on the extent of nerve damage and recovery.

The laboratory diagnosis of polio virus infection can be done by various methods, such as:

• Microscopy: Virus can be detected in stool specimens by direct electron microscopy or by immune electron microscopy. Virus is rarely demonstrated in cerebrospinal fluid (CSF), but microscopy of CSF may show lymphocytic pleocytosis.
• Virus isolation: Virus can be recovered from throat swabs, stool specimens, and occasionally CSF by cultivation on cell cultures, such as monkey kidney, human amnion, HeLa cells, Hep-2, Buffalo green monkey (BGM), MRC-5 and others. Cytopathic effects appear in 3–6 days and include cell retraction, increased refractivity, cytoplasmic granularity, and nuclear pyknosis. An isolated virus can be identified and typed by neutralization with specific antiserum.
• Serology: Demonstration of a fourfold increase of antibody titer in the serum samples collected at the time of acute illness and convalescence can support the diagnosis of paralytic poliomyelitis, especially if the patient is not vaccinated. Neutralization test and complement fixation test can be used to detect antibodies.
• Molecular diagnosis: Virus can also be identified more rapidly by polymerase chain reaction (PCR) assays using specimens from the throat, feces, or CSF. Real-time reverse transcription PCR can differentiate wild strains from vaccine-like strains (intratypic differentiation) and partial genome sequencing can confirm the poliovirus genotype and determine its likely geographic origin.

Unfortunately, there is no specific treatment or cure for polio virus infection. The main goal of treatment is to prevent or reduce the symptoms and complications of the disease, and to support the recovery of the affected nerves and muscles. Depending on the type and severity of polio, different treatment options may be used.

• For asymptomatic or abortive polio, which causes mild flu-like symptoms, the treatment is usually supportive and involves bed rest, hydration, pain relievers (such as ibuprofen or acetaminophen), and fever reducers. These measures can help ease the discomfort and speed up the recovery of the patient.
• For nonparalytic polio, which causes more severe symptoms such as meningitis, muscle weakness, and stiffness, the treatment may also include physical therapy, splints, braces, or orthopedic shoes to help with mobility and prevent deformities. Antibiotics may be prescribed to treat secondary bacterial infections that may occur.
• For paralytic polio, which causes partial or complete paralysis of one or more limbs or muscles, the treatment is more intensive and may require hospitalization. The patient may need mechanical ventilation to assist with breathing, especially if the respiratory muscles are affected. Intravenous fluids and nutrition may be given to prevent dehydration and malnutrition. Antispasmodic drugs may be used to reduce muscle spasms and pain. Physical therapy, occupational therapy, speech therapy, and rehabilitation programs may be needed to restore muscle function and prevent complications such as contractures, pressure sores, osteoporosis, or pulmonary embolism.
• For post-polio syndrome, which is a condition that affects some polio survivors years after their initial infection and causes new or worsening symptoms such as fatigue, weakness, pain, or breathing problems, the treatment is mainly symptomatic and supportive. The patient may benefit from lifestyle modifications such as regular exercise, balanced diet, stress management, energy conservation, and assistive devices. Medications such as analgesics, anti-inflammatory drugs, antidepressants, or anticholinesterase drugs may be prescribed to manage pain, inflammation, depression, or muscle weakness. Surgery may be considered in some cases to correct deformities or improve mobility.

The best way to prevent polio is by getting vaccinated against the virus. There are two types of polio vaccines available: the inactivated polio vaccine (IPV), which is given by injection and provides protection against all three types of polio virus; and the oral polio vaccine (OPV), which is given by mouth and contains weakened live virus that stimulates immunity in the gut. Both vaccines are safe and effective, but OPV may rarely cause vaccine-associated paralytic poliomyelitis (VAPP) in some recipients or their contacts. Therefore, OPV is mainly used in countries where polio is still endemic or at risk of outbreaks.

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