Poliovirus On the Web
American Roentgen Ray Society Images of Poliovirus
Poliovirus is a small, nonenveloped, positive stranded RNA virus, that belongs to the family of Picornaviridae. It is a transient inhabitant of the GI tract, where it replicates, to further infect distant regions, however, poliovirus rarely causes symptoms. Three serotypes of poliovirus, P1, P2 and P3, may be identified. Tissue tropism is dictated by extracellular and intracellular factors. The cellular receptor CD155 is the extracellular receptor for poliovirus. It may be identified in organs, such as the brain, heart, skeletal muscle and liver. Intracellular factors that influence viral replication include: polypyrimidine tract binding protein (PTB), which binds to IRES; the proteolytic processing of poliovirus proteins; and lack of an host factor for viral replication. Humans are the only natural reservoirs for poliovirus.
Poliovirus is a member of the genus enterovirus, family Picornaviridae. Enteroviruses are small, nonenveloped, positive stranded RNA viruses. Other members of the family include: Rhinovirus, Hepatovirus, Cardiovirus and Apthovirus. Poliovirus is a transient inhabitant of the gastrointestinal tract, stable at an acid pH. Disease syndromes resulting from viral spread to other secondary organs are rare. Despite this fact, these syndromes lead to severe disease complications, seldom with fatal outcomes.
There are three serotypes of poliovirus (P1, P2, and P3) that replicate efficiently in the gastrointestinal tract. There is minimal heterotypic immunity between the three serotypes. That is, immunity to one serotype does not produce significant immunity to any of the other serotypes. The poliovirus is rapidly inactivated by heat, formaldehyde, chlorine, and ultraviolet light. The characteristics of poliovirus make it a good model for viral study, namely: high viral titers, stable capsid and ease of purification, along with a low bio-safety requirement.
The genome of poliovirus consists of a single positive-sense RNA molecule, of approximately 7740 nucleotides. At the 5' end of the RNA molecule are coded 88 nucleotides that interact, to form a clover leaf structure, which is involved in the replication process. At the 3' end of the genome is encoded a poly Adenine sequence, which varies about 60 adenylate residues in length. The translation of the genome is initiated by the attachment of host cell's ribosomes to the often called internal ribosomal entry site (IRES). This is a specific RNA segment in the 5' end region of the RNA (not translated), where the host cell's translational ribosomes first attach in order to initiate viral genome replication. The understanding of this mechanism has led to the establishment of a new mechanism of protein synthesis in eukaryotes.
The cellular receptor for poliovirus was discovered after the transformation of mouse L-cells. These cells were altered with HeLa cell DNA, which led to susceptibility to poliovirus, of previously unsusceptible mice. The cDNA of the cellular receptor for poliovirus was later isolated and named CD155, or PVR. This receptor is a member of the immunoglobulin family, containing 3 Ig domains. CD155 is expressed in the following organs:
- The detection method does not differentiate variants of the receptor. Some variants, despite being detected, may not serve as receptors.
- Excess secretion of non-receptor isoforms of CD155 may compete for the virus, thereby inactivating it.
- Other ligands may compete with poliovirus for CD155.
- Physical barriers may block poliovirus access to CD155.
- Cytoplasm of certain cells may be inadequate for poliovirus replication.
- Germinal centers of tonsils
- Germinal centers of Peyer's patches
- Epithelium of Peyer's patches
- Small intestine enterocytes
- Colon enterocytes
Extracellular viral receptors are not the only determinants of tissue tropism. Genetic properties of the virus, which dictate the ability of poliovirus to replicate within a certain cell environment, are also important contributors to tissue tropism. Cellular host factors also interact with viral RNA, influencing replication. An example is polypyrimidine tract binding protein (PTB), which binds to IRES. This binding initiates a cap-independent translation of the virus, and has also been implicated in alternative splicing mechanisms. Other factors within the host cell may alter the poliovirus replication cycle:
- Proteolytic processing of poliovirus proteins
- Lack of an host factors for viral replication
- Cessation of protein synthesis within the host cell
Only human cells, and certain primate species, show receptors for poliovirus. Therefore humans are considered the only natural reservoir for poliovirus. There is no asymptomatic carrier state, except in the case of immunodeficient patients.
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