Poliovirus

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Poliovirus
Virus classification
Group: Group IV ((+)ssRNA) Family: Picornaviridae Genus: Enterovirus Species: Poliovirus

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. In 1981, the poliovirus genome was published by two different teams of researchers, one at MIT and the other at the State University of New York, Stony Brook.^[3] Because of its short genome and its simple composition—only RNA and an non-enveloped icosahedral protein coat that encapsulates it—poliovirus is widely regarded as the simplest significant virus.^[4]

Contents 1 Life cycle 2 Pathogenesis 3 Immune system avoidance 4 Serotypes 5 References

[edit] Life cycle

Poliovirus infects human cells by binding to a immunoglobulin-like receptor (PVR or CD155) on the surface of a human cell.^[5] The precise mechanism that poliovirus uses to enter the host cell has not been firmly established.^[6] It may be that binding to CD155 triggers a conformational change in the virus which allows the virus to attach to the host cell membrane, followed by the formation of a pore in the membrane through which the viral RNA is then “injected” into the host cell cytoplasm. Another hypothesis is that the virus is taken up via receptor-mediated endocytosis.^[7] By either mechanism the poliovirus entry strategy is very inefficient; it is able to initiate an infection only about 1% of the the time.^[8]

Once inside the cell, the viral RNA acts like the host messenger RNA and, uses the host's own machinery to copy itself.^[2] The virus initiates replication of new viruses via a highly structured portion of the viral genome that binds to the host translational machinery. This portion of the poliovirus genome is known as the internal ribosome entry site (IRES). The IRES is required for poliovirus replication.^[7] The genome of poliovirus is only large enough to encode about 10 genes. These genes encode for a small number of viral proteins including:^[4][8]

• 3Dpol, an RNA dependent RNA polymerase, which allows polio's RNA genome to be copied within the host cell. The entire polio genome is copied into in one long strand of protein.
• 2Apro and 3Cpro/3CDpro, proteases, that cleave the long strand of viral protein into functional products.
• A small protein (VPg) tags the virus's RNA, so that it can be differentiated from host RNA.
• Several proteins that inhibit the host cell's normal synthesis of proteins.
• Three capsid proteins, VP0, VP1 and VP3.

The assembly of new virus particles, (i.e. the packaging of progeny genomes into capsids which can survive outside the host cell) is poorly understood.^[7] Fully assembled poliovirus leaves the confines of its host cell when the cell dies, which occurs 6-10 hours following viral infection.^[8] The mechanism of release of the virus from the cell is unclear.^[2] As many as 100,000 polio virions can be released from one infected cell.^[8]

[edit] Pathogenesis

Typically, poliovirus infection involves replication of the virus within the gastrointestinal tract and subsequent shedding of the virus in feces. In 95% of cases only 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, head ache and sore throat.^[9]

In about 1-2% of poliovirus infections the virus enters 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, which leads 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,^[7] two theories, however, have been suggested to explain the viral diversion.

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).^[10] The second hypothesis suggests that the virus is transported from the muscle to the spinal cord through nerve pathways by retrograde axonal transport.^[11] 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,^[12] which may then be involved in spreading the virus from the sites of primary infection (the gut) into the circulation, and potentially to the CNS.

[edit] 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.^[4] Second, because it can replicate very rapidly - the virus overwhelms the host organs before an immune response can be mounted.^[13]

[edit] Serotypes

There are three serotypes of poliovirus, PV1 (Mahoney), PV2 (Lansing), and PV3 (Leon); each with a slightly different capsid protein. PV1 is the most common form encountered in nature, however all three forms are extremely infectious. 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.^[5] Infection with one type of poliovirus does not provide immunity against the other types, however second attacks within the same individual are extremely rare.

[edit] References