Poliovirus, the agent behind poliomyelitis, is a small RNA virus that primarily affects humans. It targets and enters specific cells, taking over their internal machinery to produce more viral particles. This manipulation disrupts normal cell functions, leading to disease.
Target Cells of Poliovirus
Poliovirus infection begins after oral ingestion, replicating in cells lining the gastrointestinal tract, including the alimentary mucosa, tonsils, and Peyer’s patches. These are primary replication hubs before the virus spreads. The virus infects these cells due to a specific surface protein: the poliovirus receptor (PVR), or CD155.
CD155 is a transmembrane protein. Poliovirus binds to a specific domain (D1) on this receptor, present on susceptible cells. Most infections stay in the gut, but in a small percentage of cases, the virus can spread through the bloodstream to the central nervous system.
In the central nervous system, poliovirus targets motor neurons, specialized nerve cells in the anterior horn of the spinal cord and brainstem. These neurons transmit signals from the brain to skeletal muscles for voluntary movement. Their vulnerability to poliovirus stems from the CD155 receptor on their surfaces, allowing viral entry.
Viral Invasion and Cellular Takeover
Poliovirus attaches to the CD155 receptor on the host cell surface. This binding changes the virus’s protein shell (capsid), releasing its genetic material into the cell’s cytoplasm. The virus enters the cell, often through receptor-mediated endocytosis, where the cell engulfs the virus in a small vesicle.
Once inside the cytoplasm, poliovirus uncoats, releasing its single-stranded positive-sense RNA genome. This viral RNA is directly recognized by host cell ribosomes due to its internal ribosome entry site (IRES). The host cell’s machinery translates this viral RNA into a single polyprotein. Viral proteases then cleave this polyprotein into individual functional viral proteins, including those for replication and forming new viral particles.
The viral RNA-dependent RNA polymerase replicates the viral genome. It uses positive-sense RNA as a template to create complementary negative-sense RNA strands, which serve as templates for synthesizing new positive-sense RNA copies. These new RNA genomes and viral proteins assemble into new viral particles. Assembled polioviruses are released from the host cell, usually within 4 to 6 hours, often involving lysis, or bursting, of the infected cell. A single infected cell can release up to 10,000 new virus particles upon lysis.
Cellular Impact and Disease
The poliovirus replication cycle within a host cell is detrimental, leading to cellular damage and destruction. As the virus redirects cell resources to produce its components, it disrupts normal metabolic processes, including cellular protein and RNA synthesis. This hijacking results in a cytopathic effect, causing visible changes and damage to the infected cell. The accumulation of new viral particles and disruption of cellular functions lead to the lysis, or bursting, of the host cell.
When this cellular destruction occurs in motor neurons, the consequences can be severe. Poliovirus specifically targets motor neuron cell bodies in the anterior horn of the spinal cord. The destruction of these neurons interrupts signals from the brain to skeletal muscles, which are necessary for voluntary movement. This interruption can result in muscle weakness and, in severe cases, acute flaccid paralysis. Affected muscles, deprived of nerve signals, lose function and can atrophy.
Most poliovirus infections are asymptomatic or cause only mild, non-paralytic symptoms. Less than 1% of infections result in paralytic poliomyelitis. When paralysis occurs, it is a direct consequence of irreversible motor neuron damage and death. The inability of affected nerve cells to regenerate means the loss of muscle function can be permanent.
Polio Cells in Scientific Advancement
Growing poliovirus in laboratory cell cultures marked a breakthrough in understanding the virus and developing vaccines. Before this, studying poliovirus relied on animal models, which were costly, ethically complex, and often yielded inconsistent results. In 1949, John Enders, Thomas Weller, and Frederick Robbins successfully cultivated poliovirus in non-nervous human tissue in a test tube, an effort recognized with a Nobel Prize. This demonstrated the virus could be grown outside live animals, paving the way for controlled research.
Jonas Salk and his team at the University of Pittsburgh found that poliovirus could be propagated on a large scale using monkey kidney cells. These cell cultures provided an abundant virus source, enabling scientists to study its life cycle, interaction with host cells, and behavior. Mass production of poliovirus in these cell lines aided the development of the inactivated polio vaccine (IPV). The virus grown in these cultures could be chemically inactivated, creating a safe vaccine that induced immunity without causing disease.
HeLa cells, derived from Henrietta Lacks’ cervical cancer cells in 1951, also proved instrumental. HeLa cells could divide indefinitely in a laboratory setting, making them an “immortal” cell line. Scientists discovered HeLa cells were susceptible to poliovirus infection and could produce vast quantities of the virus. This prolific nature made HeLa cells invaluable for large-scale vaccine testing and production, accelerating the development and widespread distribution of both inactivated and oral polio vaccines. The use of these cell lines revolutionized virology, providing the foundation for controlling and nearly eradicating poliomyelitis globally.