Pathogenesis
The primary determinant of infection for any virus is its ability to enter a cell and produce additional infectious particles. The presence of CD155 is thought to define the animals and tissues that can be infected by poliovirus. CD155 is found (outside of laboratories) only on the cells of humans, higher primates, and Old World monkeys. Poliovirus is however strictly a human pathogen, and does not naturally infect any other species (although chimpanzees and Old World monkeys can be experimentally infected).
The CD155 gene appears to have been subject to positive selection. The protein has several domains of which domain D1 contains the polio virus binding site. Within this domain 37 amino acids are responsible for binding the virus.
Poliovirus is an enterovirus. Infection occurs via the fecal-oral route, meaning that one ingests the virus and viral replication occurs in the alimentary tract. Virus is shed in the feces of infected individuals. In 95% of cases only a primary, transient presence of viremia (virus in the bloodstream) occurs, and the poliovirus infection is asymptomatic. In about 5% of cases, the virus spreads and replicates in other sites such as brown fat, reticuloendothelial tissue, and muscle. The sustained viral replication causes secondary viremia and leads to the development of minor symptoms such as fever, headache and sore throat. Paralytic poliomyelitis occurs in less than 1% of poliovirus infections. Paralytic disease occurs when the virus enters the central nervous system (CNS) and replicates in motor neurons within the spinal cord, brain stem, or motor cortex, resulting in the selective destruction of motor neurons leading to temporary or permanent paralysis. In rare cases, paralytic poliomyelitis leads to respiratory arrest and death. In cases of paralytic disease, muscle pain and spasms are frequently observed prior to onset of weakness and paralysis. Paralysis typically persists anywhere from days to weeks prior to recovery.
In many respects the neurological phase of infection is thought to be an accidental diversion of the normal gastrointestinal infection. The mechanisms by which poliovirus enters the CNS are poorly understood. Three non-mutually exclusive hypotheses have been suggested to explain its entry. All theories require primary viremia. The first hypothesis predicts that virions pass directly from the blood into the central nervous system by crossing the blood brain barrier independent of CD155. A second hypothesis suggests that the virions are transported from peripheral tissues that have been bathed in the viremic blood, for example muscle tissue, to the spinal cord through nerve pathways via retrograde axonal transport. A third hypothesis is that the virus is imported into the CNS via infected monocytes or macrophages.
Poliomyelitis is a disease of the central nervous system. However, CD155 is believed to be present on the surface of most or all human cells. Therefore receptor expression does not explain why poliovirus preferentially infects certain tissues. This suggests that tissue tropism is determined after cellular infection. Recent work has suggested that the type I interferon response (specifically that of interferon alpha and beta) is an important factor that defines which types of cells support poliovirus replication. In mice expressing CD155 (through genetic engineering) but lacking the type I interferon receptor, poliovirus not only replicates in an expanded repertoire of tissue types, but these mice are also able to be infected orally with the virus.
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