Poliovirus is a human enterovirus in the family of Picornaviridae, and the causative agent in poliomyelitis.^[1] It is a small RNA virus (ribonucleic acid), about 300 Ångström in diameter, with a single-stranded positive-sense RNA genome that is about 7500 bases long.^[2] Poliovirus was isolated in 1908 by Karl Landsteiner and Erwin Popper.^[3] In 1981, the poliovirus genome was published by two different teams of researchers— by Vincent Racaniello and David Baltimore at MIT^[4] and the other led by Naomi Kitamura at the State University of New York, Stony Brook.^[5] Because of its short genome and its simple composition—only RNA and a non-enveloped icosahedral protein coat that encapsulates it—poliovirus is widely regarded as the simplest significant virus.^[6] Pubtjyujgykkjkjj File links The following pages link to this file: Polio Rhinovirus Enterobacteria phage T2 HTDV Reoviridae Picornaviridae Human respiratory syncytial virus Papillomavirus Wikipedia:Stub and disambiguation message example Wikipedia:Template messages/Stubs Ebola Reston Wikipedia:Stub categories Vibrio vilnificus Virus cancer link Wikipedia:Template messages/All Enterovirus Wikipedia:Template... A section of a cell of Bacillus subtilis, taken with a Tecnai T-12 TEM. The scale bar is 200nm. ... A micrograph is a photograph or similar image taken through a microscope or similar device to show a magnified image of an item. ... A common alternate meaning of virus is computer virus. ... Virus classification involves naming and placing viruses into a taxonomic system. ... An RNA virus is a virus that either uses RNA as its genetic material, or whose genetic material passes through an RNA intermediate during replication. ... Genera Enterovirus Rhinovirus Hepatovirus Cardiovirus Apthovirus Parechovirus Erbovirus Kobuvirus Teschovirus Picornaviruses are viruses that belong to the family Picornaviridae. ... Species Bovine enterovirus Coxsackie virus Human enterovirus A Human enterovirus B Human enterovirus C Human enterovirus D Human enterovirus E Poliovirus Porcine enterovirus A Porcine enterovirus B Swine vesicular disease virus The enteroviruses are a genus of (+)ssRNA viruses associated with several human and mammalian diseases. ... This article is about the disease. ... Species Bovine enterovirus Coxsackie virus Human enterovirus A Human enterovirus B Human enterovirus C Human enterovirus D Human enterovirus E Poliovirus Porcine enterovirus A Porcine enterovirus B Swine vesicular disease virus The enteroviruses are a genus of (+)ssRNA viruses associated with several human and mammalian diseases. ... Genera Enterovirus Rhinovirus Hepatovirus Cardiovirus Apthovirus Parechovirus Erbovirus Kobuvirus Teschovirus Picornaviruses are viruses that belong to the family Picornaviridae. ... This article is about the disease. ... An RNA virus is a virus that either uses RNA as its genetic material, or whose genetic material passes through an RNA intermediate during replication. ... Ribonucleic acid (RNA) is a nucleic acid consisting of a string of covalently-bound nucleotides. ... An Ã¥ngström or aangstroem (the official transliteration), or angstrom (symbol Ã…) is a non-SI unit of length that is internationally recognized, equal to 0. ... Sense, when applied in a molecular biology context, is a general concept used to compare the polarity of nucleic acid molecules, particularly RNA, to other nucleic acid molecules. ... In biology the genome of an organism is the whole hereditary information of an organism that is encoded in the DNA (or, for some viruses, RNA). ... Karl Landsteiner Karl Landsteiner (June 14, 1868 – June 26, 1943), was an Austrian biologist and physician. ... Vincent R. Racaniello Vincent R. Racaniello (born January 2, 1953 in Patterson, New Jersey. ... David Baltimore (b. ... The Massachusetts Institute of Technology (MIT) is a private, coeducational research university located in Cambridge, Massachusetts. ... Stony Brook University Stony Brook University (SBU) or the University at Stony Brook (USB), or the State University of New York at Stony Brook (SUNYSB), located in Stony Brook, New York, USA, is one of the premier public universities in the United States with more than 21,000 students enrolled. ... Many viruses (e. ... An icosahedron [ˌaıkəsəhiːdrən] noun (plural: -drons, -dra [-drə]) is a polyhedron having 20 faces. ... A capsid is the outer shell of a virus. ...

Origin and serotypes

There are three serotypes of poliovirus, PV1 (Mahoney), PV2 (Lansing), and PV3 (Leon); each with a slightly different capsid protein. Capsid proteins define cellular receptor specificity and virus antigenicity. PV1 is the most common form encountered in nature, however all three forms are extremely infectious.^[3] Serotypes refer to a group of related microorganisms or viruses distinguished by responses to different antigens. ... A capsid is the outer shell of a virus. ... Infection is also the title of an episode of the television series Babylon 5; see Infection (Babylon 5). ...

All three forms of poliovirus are structurally similar to other human enteroviruses, coxsackieviruses, echoviruses, and to human rhinoviruses, which also use immunoglobulin-like molecules to recognize and enter host cells.^[7] Phylogenetic analysis of the RNA and protein sequences of poliovirus suggests that PV may have evolved from a C-cluster coxsackie A virus ancestor, arising through a mutation within the capsid.^[8] The distinct speciation of poliovirus probably occurred as a result of change in cellular receptor specificity from intercellular adhesion molecule-1 (ICAM-1), used by C-cluster coxsackie A viruses, to CD155; leading to a change in pathogenicity, and allowing the virus to infect nervous tissue. Coxsackie A virus is a cytolytic virus of the Picornaviridae family, a enterovirus (a group containing the polioviruses, coxsackieviruses, and echoviruses). ... An echovirus is a type of RNA virus that belongs to the Enterovirus and the Picornaviridae virus family. ... Species Human rhinovirus A (HRV-A) Human rhinovirus B (HRV-B) Rhinovirus (from the Greek rhin-, which means nose) is a genus of the Picornaviridae family of viruses. ... A phylogeny (or phylogenesis) is the origin and evolution of a set of organisms, usually of a species. ... Coxsackie (virus) is a cytolytic virus of the Picornaviridae family, an enterovirus (a group containing the polioviruses, coxsackieviruses, and echoviruses). ... A group of organisms is said to have common descent if they have a common ancestor. ... Charles Darwins first sketch of an evolutionary tree from his First Notebook on Transmutation of Species (1837) Speciation is the evolutionary process by which new biological species arise. ... Cell Adhesion Molecules (CAMs) are proteins located on the cell surface involved with the binding with other cells or with the extracellular matrix (ECM) in the process called cell adhesion. ... CD155 is a Type I transmembrane glycoprotein in the immunoglobulin superfamily. ...

Life cycle

Poliovirus infects human cells by binding to an immunoglobulin-like receptor CD155, also known as the poliovirus receptor (PVR),^[9][7] on the cell surface.^[10] Interaction of poliovirus and CD155 facilitates an irreversible conformational change of the viral particle necessary for viral entry.^[11][12] The precise mechanism poliovirus uses to enter the host cell has not been firmly established.^[13] Attached to the host cell membrane, entry of the viral nucleic acid was thought to occur one of two ways: via the formation of a pore in the plasma membrane through which the RNA is then “injected” into the host cell cytoplasm, or that the virus is taken up by receptor-mediated endocytosis.^[14] Recent experimental evidence supports the latter hypothesis and suggests that poliovirus binds to CD155 and is taken up via endocytosis. Immediately after internalization of the particle, the viral RNA is released.^[15] However, any mechanism by which poliovirus enters the cell is very inefficient; as infection is initiated only about 1% of the time.^[16] Schematic of antibody binding to an antigen An antibody is a protein complex used by the immune system to identify and neutralize foreign objects like bacteria and viruses. ... CD155 is a Type I transmembrane glycoprotein in the immunoglobulin superfamily. ... Look up cell membrane in Wiktionary, the free dictionary. ... A pore, in general, is some form of opening, usually very small. ... It has been suggested that Cytoplast be merged into this article or section. ... Receptor-mediated endocytosis (RME) is a process by which cells internalize molecules (endocytosis) into a cell by the inward budding of plasma membrane vesicles containing proteins with receptor sites specific to the molecules being internalized. ...

The structural appearance of Poliovirus.

Poliovirus is a positive stranded RNA virus. Thus the genome enclosed within the viral particle can be used as messenger RNA. Upon entry into the cell, the cell's translation machinery translates the viral RNA, selectively producing virus–specific proteins. Infection with poliovirus results in inhibition of cellular protein synthesis suggesting that translation of the viral RNA must occur differently. Unlike most cellular mRNAs the 5' end of poliovirus RNA is extremely long, over 700 nucleotides, and is highly structured. It is this region of the viral genome which directs translation of the virus RNA. Alterations of this region prevent viral protein production. Ultimately it was demonstrated that translation of poliovirus RNA occurs via an internal ribosome entry site (IRES).^[17][18][19] Poliovirus mRNA is translated as one polypeptide. This polypeptide is cleaved into 10 individual viral proteins, including:^[6][16] Image File history File links No higher resolution available. ... Image File history File links No higher resolution available. ... The life cycle of an mRNA in a eukaryotic cell. ... An internal ribosome entry site, or IRES, is a DNA sequence that allows for translation initiation in the middle of the mRNA. Usually, in eukaryotes, translation can only be initiated at the 5 end of the mRNA molecule, since 5 cap recognition is required for the assembly of the initiation...

• 3D^pol, an RNA dependent RNA polymerase.
• 2A^pro and 3C^pro/3CD^pro, proteases which cleave the viral polypeptide.
• VPg (3B), a small protein that binds viral RNA and is necessary for synthesis of viral positive and negative strand RNA.
• 2BC, 2B, 2C, 3AB, 3A, 3B proteins which comprise the protein complex needed for virus replication.
• VP0, VP1, VP2, VP3, VP4 proteins of the viral capsid.

The assembly of new virus particles, (i.e. the packaging of progeny genome into a capsid which can survive outside the host cell) is poorly understood.^[14] Fully assembled poliovirus leaves the confines of its host cell 4 to 6 hours following initiation of infection in cultured mammalian cells.^[20] The mechanism of viral release from the cell is unclear,^[2] but each dying cell can release as many as 10,000 polio virions.^[20] RNA dependent RNA polymerase, or RDRP, is an enzyme that catalyzes the replication of RNA from an RNA template. ... Proteases (proteinases, peptidases, or proteolytic enzymes) are enzymes that break peptide bonds between amino acids of proteins. ... A common alternate meaning of virus is computer virus. ...

Pathogenesis

Electron micrograph of poliovirus.

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 could be infected by poliovirus. CD155, which is able to interact with poliovirus, is found only on the cells of humans, higher primates, and Old World monkeys. Poliovirus however, is strictly a human pathogen, and does not naturally infect any other species.^[21] CD155 is believed to be present on the surface of most, if not all, human cells and thus, it's expression does not explain why poliovirus causes disease within the central nervous system. Image File history File links Download high resolution version (724x1000, 690 KB) File links The following pages on the English Wikipedia link to this file (pages on other projects are not listed): Virus ... Image File history File links Download high resolution version (724x1000, 690 KB) File links The following pages on the English Wikipedia link to this file (pages on other projects are not listed): Virus ... An electron micrograph is a micrograph made with an electron microscope. ... For the ecclesiastical use of this term, see primate (religion) Families 13, See classification A primate is any member of the biological order Primates, the group that contains all lemurs, monkeys, and apes, including humans. ... Subfamilies Cercopithecinae - 11 genera Colobinae - 10 genera The Old World monkeys or Cercopithecidae are a group of primates, falling in the superfamily Cercopithecoidea in the clade Catarrhini. ...

Poliovirus is an enterovirus. Infection occurs via the fecal-oral route; meaning that one ingests the virus and it is within the alimentary tract that virus replication occurs. Virus is shed in the feces of infected individuals. In 95% of cases only a primary, transient presence of the virus in the bloodstream occurs (called a viremia) and the poliovirus infection is asymptomatic. In about 5% of cases, the virus spreads, and replicates in other sites such as brown fat, the reticuloendothelial tissues, and muscle. This sustained replication causes a secondary viremia, and leads to the development of minor symptoms such as fever, headache and sore throat.^[22] Many diseases can be passed when fecal particles from one host are introduced into the mouth of another potential host. ... Viremia is a condition where viruses enter the bloodstream. ... In medicine, a disease is asymptomatic when it is at a stage where the patient does not experience symptoms. ... Brown fat is a type of adipose tissue present in many newborn or hibernating mammals. ... The reticuloendothelial system (RES), part of the immune system, consists of the phagocytic cells located in reticular connective tissue, primarily monocytes and macrophages. ... A top-down view of skeletal muscle Muscle (from Latin musculus little mouse [1]) is contractile tissue of the body and is derived from the mesodermal layer of embryonic germ cells. ...

In about 1-2% of poliovirus infections 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, and leading to either temporary or permanent paralysis and, in rare cases, to respiratory arrest and death. 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 spreads to the CNS are poorly understood,^[14] two theories, however, have been suggested to explain the viral diversion. A diagram showing the CNS: 1. ... In vertebrates, the term motor neuron (or motoneuron) classically applies to neurons located in the central nervous system (CNS) which project their axons outside the CNS and directly or indirectly control muscles. ... The Spinal cord nested in the vertebral column. ... The brain stem is the lower part of the brain, adjoining and structurally continuous with the spinal cord. ... To meet Wikipedias quality standards, this article or section may require cleanup. ... This article does not cite any references or sources. ... Respiratory arrest is the cessation of the normal tidal flow of the lungs due to paralysis of the diaphragm, collapse of the lung or any number of respiratory failures. ... Neurology is a branch of medicine dealing with disorders of the central and peripheral nervous systems. ... For the Physics term GUT, please refer to Grand unification theory The gastrointestinal or digestive tract, also referred to as the GI tract or the alimentary canal or the gut, is the system of organs within multicellular animals which takes in food, digests it to extract energy and nutrients, and...

The first hypothesis is that the virus passes directly from the blood into the central nervous system by crossing the blood brain barrier, without binding to its cellular receptor (CD155).^[23] The second hypothesis suggests that the virus is transported from the muscle to the spinal cord through nerve pathways by retrograde axonal transport.^[24] Both theories require that the virus be present in the blood (viremia), and it has been demonstrated that poliovirus can bind to and replicate within primary human monocytes in the blood.^[25] The infected monocytes may then be involved in spreading the virus from the sites of primary infection (the gut) into the circulation, and potentially to the CNS. Human blood smear: a - erythrocytes; b - neutrophil; c - eosinophil; d - lymphocyte. ... The blood-brain barrier is a physical barrier between the blood vessels in the central nervous system, and the central nervous system itself. ... This article is about retrograde motion. ... An axon or nerve fiber, is a long, slender projection of a nerve cell, or neuron, that conducts electrical impulses away from the neurons cell body or soma. ... MONOCYTES: Plural of monocyte. ...

Immune system avoidance

Poliovirus uses two key mechanisms to evade the immune system. First, it is capable of surviving the highly acidic conditions of the gastrointestinal tract, allowing the virus to infect the host and spread throughout the body via the lymphatic system.^[6] Second, because it can replicate very rapidly - the virus overwhelms the host organs before an immune response can be mounted.^[4] A scanning electron microscope image of a single neutrophil (yellow), engulfing anthrax bacteria (orange). ... The correct title of this article is . ... Upper and Lower gastrointestinal tract The gastrointestinal tract (GI tract), also called the digestive tract, or the alimentary canal, is the system of organs within multicellular animals that takes in food, digests it to extract energy and nutrients, and expels the remaining waste. ... The human lymphatic system The lymphatic system is a complex network of lymphoid organs, lymph nodes, lymph ducts, lymphatic tissues, lymph capillaries and lymph vessels that produce and transport lymph fluid from tissues to the circulatory system. ...

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.^[20] Infection with one serotype of poliovirus does not provide immunity against the other serotypes, however second attacks within the same individual are extremely rare. Wikipedia does not yet have an article with this exact name. ... This article or section contains too much jargon and may need simplification or further explanation. ... IGA may stand for: Koji Igarashi, a video game producer Interactive genetic algorithm International Geothermal Association Independent Glass Association International Gothic Association International Gamers Award International Goat Association Irish Games Association Irish Geological Association ImmunoGlobulin A - see IgA nephritis which is a renal disease IGA (supermarkets) Independent Grocers Association or... Schematic of antibody binding to an antigen An antibody is a protein complex used by the immune system to identify and neutralize foreign objects like bacteria and viruses. ... IGM might be an acronym or abbreviation for: The polymeric immunoglobulin, IgM International Grandmaster, a chess ranking intergalactic medium Intragroup medium - see: Intracluster medium IG Metall - the dominant German metalworkers union IGM is an acronym created by Robinson Technologies for several early BBS door games, including Legend of the Red... Immunity is a medical term that describes a state of having sufficient biological defenses to avoid infection, disease, or other unwanted biological invasion. ...

PVR transgenic mouse

Poliovirus is one of the most well-characterized viruses. 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 mouse model of polio was developed when two laboratories established lines of mice engineered to express a human receptor to poliovirus (hPVR).^[26][27] An iconic image of genetic engineering; this autoluminograph from 1986 of a glowing transgenic tobacco plant bearing the luciferase gene, illustrating the possibilities of genetic engineering. ...

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.^[28] 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.^[29] A genetically modified organism is an organism whose genetic material has been deliberately altered. ... An intravenous drip in a hospital Intravenous therapy or IV therapy is the administration of liquid substances directly into a vein. ... Intramuscular injection is an injection of a substance directly into a muscle. ... The Spinal cord nested in the vertebral column. ... For other uses, see Brain (disambiguation). ... Histopathology is a field of pathology which specialises in the histologic study of diseased tissue. ...

Three distinct types of TgPVR mice have been well studied:^[30]

• 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.^[31]
• 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 forth 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.^[31]

The development of the TgPVR mouse has also 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.^[32] Figure 1: A representation of a condensed eukaryotic chromosome, as seen during cell division. ... (adj. ... The mucous membranes (or mucosa) are linings of ectodermic origin, covered in epithelium, that line various body cavities and internal organs. ... In genetics, complementary DNA (cDNA) is single-stranded DNA synthesized from a mature mRNA template. ... G-Actin (PDB code: 1j6z). ... A promoter is a regulatory region of DNA located upstream (towards the 5 region) of a gene, providing a control point for regulated gene transcription. ... This article is about the disease. ... The World Health Organization (WHO) is a specialized agency of the United Nations (UN) that acts as a coordinating authority on international public health. ...

Artificial synthesis

In 2002 researchers from SUNY Stony Brook succeeded in synthesizing poliovirus from its chemical code, producing the world's first synthetic virus.^[33] Using the published genetic code, the scientists first converted poliovirus's RNA sequence into a DNA sequence, and short fragments of the DNA sequence were assembled. The complete virus 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. Stony Brook University Stony Brook University (SBU) or the University at Stony Brook (USB), or the State University of New York at Stony Brook (SUNYSB), located in Stony Brook, New York, USA, is one of the premier public universities in the United States with more than 21,000 students enrolled. ... For a non-technical introduction to the topic, see Introduction to Genetics. ... Gene synthesis is the process of synthesizing an artificially designed gene into a physical DNA sequence. ... A marker gene is used in molecular biology to determine if a piece of DNA has been successfully inserted into the host organism. ... Ribbon diagram of the enzyme TIM, surrounded by the space-filling model of the protein. ...

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 less lethal than the original virus.^[34]

References

A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ... A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ... A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ... A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ...

External links

• ICTVdb virus classification