Poliovirus Totally Explained

Everything about Polio Virus totally explained

Poliovirus, the causative agent of poliomyelitis, is a human enterovirus and member of the family of Picornaviridae. Poliovirus is composed of a RNA genome and a protein capsid. The genome is single-stranded positive-sense RNA genome that's about 7500 nucleotides long. The viral particle is about 300 Ångström in diameter with icosahedral symmetry. 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.
Poliovirus was first isolated in 1909 by Karl Landsteiner and Erwin Popper. In 1981, the poliovirus genome was published by two different teams of researchers— by Vincent Racaniello and David Baltimore at MIT and by Naomi Kitamura and others at the State University of New York, Stony Brook. Poliovirus is one of the most well-characterized viruses, and has become a useful model system for understanding the biology of RNA viruses.

Origin and serotypes

There are three serotypes of poliovirus, PV1 (Mahoney or Brunhilde), 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. 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.

Life cycle

Poliovirus infects human cells by binding to an immunoglobulin-like receptor, CD155, (also known as the poliovirus receptor (PVR)) on the cell surface. Interaction of poliovirus and CD155 facilitates an irreversible conformational change of the viral particle necessary for viral entry. The precise mechanism poliovirus uses to enter the host cell hasn't been firmly established. 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. 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. However, any mechanism by which poliovirus enters the cell is very inefficient; as an infection is initiated only about 1% of the time.
   Poliovirus is a positive stranded RNA virus. Thus the genome enclosed within the viral particle can be used as messenger RNA and immediately translated by the host cell. Upon entry the virus hijacks the cell's translation machinery; causing inhibition of cellular protein synthesis in favor of virus–specific protein production. 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 viral RNA, and 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).
   Poliovirus mRNA is translated as one long polypeptide. This polypeptide is then cleaved into approximately 10 individual viral proteins, including: The mechanism of viral release from the cell is unclear,
   Poliovirus is an enterovirus. Infection occurs via the fecal-oral route; meaning that one ingests the virus and it's 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. Paraltyic poliomyletis 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 either temporary or permanent paralysis and, in rare cases, to respiratory arrest and death. In many respects this neurological phase of infection is thought to be an accidental diversion of the normal gastrointestinal infection. A second hypothesis suggests that the virus is transported from the muscle to the spinal cord through nerve pathways by retrograde axonal transport. A third hypothesis is that the virus is imported into the CNS by infected monocytes or macrophages. In mice expressing CD155 but lacking the type I interferon receptor, poliovirus not only replicates in tissues it normally would not, but these mice are also able to be infected orally with the virus.

Immune system avoidance

Poliovirus uses two key mechanisms to evade the immune system. First, it's 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.
   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.
   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 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.

Cloning and synthesis

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 researchers at SUNY Stony Brook 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. This whole painstaking process took two years. 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. 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.
Further Information

Get more info on 'Polio Virus'.

External Link Exchanges

Do you know how hard it is to get a link from a large encyclopaedia? Well we're different and will prove it. To get a link from us just add the following HTML to your site on a relevant page:

<a href="http://poliovirus.totallyexplained.com">Poliovirus Totally Explained</a>

Then simply click through this link from your web page. Our crawlers will verify your link, extract the title of your web page and instantly add a link back to it. If you like you can remove the words Totally Explained and embed the link in article text.
As long as your link remains in place, we'll keep our link to you right here. Please play fair - our crawlers are watching. Your site must be closely related to this one's topic. Any kind of spamming, dubious practises or removing the link will result in your link from us being dropped and, potentially, your whole site being banned.