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. this is a very rare event in babies, who still have anti-poliovirus antibodies acquired from their mothers. 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 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 nonmutually 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. immune system avoidance cd155 molecules complexed with a poliovirus particle. reconstructed image from cryo-electron microscopy. poliovirus uses two key mechanisms to evade the immune system. first, it can survive the highly acidic conditions of the stomach, allowing the virus to infect the host and spread throughout the body via the lymphatic system. second, because it can replicate very quickly, the virus overwhelms the host organs before an immune response can be mounted. if detail is given at the attachment phase; poliovirus with canyons on the virion surface have virus attachment sites located in pockets at the canyon bases. the canyons are too narrow for access by antibodies, so the virus attachment sites are protected from the host's immune surveillance, while the remainder of the virion surface can mutate to avoid the host's immune response. individuals who are exposed to poliovirus, either through infection or by immunization with polio vaccine, develop immunity. in immune individuals, antibodies against poliovirus are present in the tonsils and gastrointestinal tract (specifically iga antibodies) and are able to block poliovirus replication; igg and igm antibodies against poliovirus can prevent the spread of the virus to motor neurons of the central nervous system. infection with one serotype of poliovirus does not provide immunity against the other serotypes; however, second attacks within the same individual are extremely rare. pvr transgenic mouse although humans are the only known natural hosts of poliovirus, monkeys can be experimentally infected and they have long been used to study poliovirus. in 1990–91, a small animal model of poliomyelitis was developed by two laboratories. mice were engineered to express a human receptor to poliovirus (hpvr). unlike normal mice, transgenic poliovirus receptor (tgpvr) mice are susceptible to poliovirus injected intravenously or intramuscularly, and when injected directly into the spinal cord or the brain. upon infection, tgpvr mice show signs of paralysis that resemble those of poliomyelitis in humans and monkeys, and the central nervous systems of paralyzed mice are histocytochemically similar to those of humans and monkeys. this mouse model of human poliovirus infection has proven to be an invaluable tool in understanding poliovirus biology and pathogenicity. three distinct types of tgpvr mice have been well studied: in tgpvr1 mice, the transgene encoding the human pvr was incorporated into mouse chromosome 4. these mice express the highest levels of the transgene and the highest sensitivity to poliovirus. tgpvr1 mice are susceptible to poliovirus through the intraspinal, intracerebral, intramuscular, and intravenous pathways, but not through the oral route. tgpvr21 mice have incorporated the human pvr at chromosome 13. these mice are less susceptible to poliovirus infection through the intracerebral route, possibly because they express decreased levels of hpvr. tgpvr21 mice have been shown to be susceptible to poliovirus infection through intranasal inoculation, and may be useful as a mucosal infection model. in tgpvr5 mice, the human transgene is located on chromosome 12. these mice exhibit the lowest levels of hpvr expression and are the least susceptible to poliovirus infection. recently, a fourth tgpvr mouse model was developed. these "cpvr" mice carry hpvr cdna, driven by a β-actin promoter, and have proven susceptible to poliovirus through intracerebral, intramuscular, and intranasal routes. in addition, these mice are capable of developing the bulbar form of polio after intranasal inoculation. the development of the tgpvr mouse has had a profound effect on oral poliovirus vaccine (opv) production. previously, monitoring the safety of opv had to be performed using monkeys, because only primates are susceptible to the virus. in 1999, the world health organization approved the use of the tgpvr mouse as an alternative method of assessing the effectiveness of the vaccine against poliovirus type-3. in 2000, the mouse model was approved for tests of vaccines against type-1 and type-2 poliovirus. cloning and synthesis model of poliovirus-binding cd155 (shown in purple) in 1981, racaniello and baltimore used recombinant dna technology to generate the first infectious clone of an animal rna virus, poliovirus. dna encoding the rna genome of poliovirus was introduced into cultured mammalian cells and infectious poliovirus was produced. creation of the infectious clone propelled understanding of poliovirus biology, and has become a standard technology used to study many other viruses. in 2002, eckard wimmer's group at stony brook university succeeded in synthesizing poliovirus from its chemical code, producing the world's first synthetic virus. scientists first converted poliovirus's published rna sequence, 7741 bases long, into a dna sequence, as dna was easier to synthesize. short fragments of this dna sequence were obtained by mail-order, and assembled. the complete viral genome was then assembled by a gene synthesis company. nineteen markers were incorporated into the synthesized dna, so that it could be distinguished from natural poliovirus. enzymes were used to convert the dna back into rna, its natural state. other enzymes were then used to translate the rna into a polypeptide, producing functional viral particle. this whole painstaking process took two years. the newly minted synthetic virus was injected into pvr transgenic mice, to determine if the synthetic version was able to cause disease. the synthetic virus was able to replicate, infect, and cause paralysis or death in mice. however, the synthetic version was between 1,000 and 10,000 times weaker than the original virus, probably due to one of the added markers. modification for therapies a modification of the poliovirus, called pvsripo, was tested in early clinical trials as a possible treatment for cancer.