Poliovirus: Difference between revisions
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This polypeptide is then cleaved into approximately 10 individual viral proteins, including:<ref name = Goodsell /><ref name= Chan/> | This polypeptide is then cleaved into approximately 10 individual viral proteins, including:<ref name = Goodsell /><ref name= Chan/> | ||
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*''VP0, VP1, VP2, VP3, VP4'' proteins of the viral capsid. | *''VP0, VP1, VP2, VP3, VP4'' proteins of the viral capsid. | ||
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.<ref name=Bodian_1965>{{cite book |author = Bodian D and Horstmann DH |title=Polioviruse |publisher=Lippincott |location=Philadelphia, Penn |year=1969 |pages= 430-473}}</ref> 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.<ref>{{cite journal |author=Sabin A |title=Pathogenesis of poliomyelitis; reappraisal in the light of new data |journal=Science |volume=123 |issue=3209 |pages=1151-7 |year=1956 |pmid=13337331}}</ref> Paraltyic poliomyletis occurs in less than 1% of poliovirus infections. Paralyitic disease occurs when the virus enters the [[central nervous system]] (CNS) and replicates in [[motor neuron]]s 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.<ref name= Mueller/> | 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.<ref name=Bodian_1965>{{cite book |author = Bodian D and Horstmann DH |title=Polioviruse |publisher=Lippincott |location=Philadelphia, Penn |year=1969 |pages= 430-473}}</ref> 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.<ref>{{cite journal |author=Sabin A |title=Pathogenesis of poliomyelitis; reappraisal in the light of new data |journal=Science |volume=123 |issue=3209 |pages=1151-7 |year=1956 |pmid=13337331}}</ref> Paraltyic poliomyletis occurs in less than 1% of poliovirus infections. Paralyitic disease occurs when the virus enters the [[central nervous system]] (CNS) and replicates in [[motor neuron]]s 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.<ref name= Mueller/> | ||
Revision as of 19:54, 29 August 2014
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: João André Alves Silva, M.D. [2]
Overview
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 extracellualar 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.
Taxonomy
Viruses; ssRNA viruses; ssRNA positive-strand viruses, no DNA stage; Picornavirales; Picornaviridae; Enterovirus; Poliovirus[1]
Biology
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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.[3][4] Enteroviruses in general do not cause disease, or are responsible for mild symptoms. Disease syndromes resulting from viral spread to other secondary regions are rare. Despite rare, these syndromes may lead to severe disease complications, seldom with fatal outcomes.
There are three poliovirus serotype (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 the other serotypes. The poliovirus is rapidly inactivated by heat, formaldehyde, chlorine, and ultraviolet light.[3]
The characteristics of poliovirus make it a good model for viral study, specifically: high viral titers, stable capsid and ease of purification, along with a low bio-safety requirement.[4]
Structure
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.[4] At the 3' end of the genome is encoded a poly Adenine sequence, which varies about 60 adenylate residues in length.[4] The translation of the genome is initiated by the attachment of the 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.[4]
Tropism
Extra-Cellular Tissue Tropism
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:[4]
However, viral replication does not occur on all CD155-expressing cells. Possible explanations include:[4]
- The detection method does not differentiate variants of the receptor. Some variants, despite detected, may not serve as receptor.
- Excess secretion of non-receptor isoforms of CD155 may compete for the virus, thereby inactivating the virus.
- 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.
CD155 positive tissues involved in the pathogenesis of the virus, include:[4]
- Germinal centers of tonsils
- Germinal centers of Peyer's patches
- Epithelium of Peyer's patches
- Small intestine enterocytes
- Colon enterocytes
Intra-Cellular Tissue Tropism
Extra-cellular 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 an important contributor for tropism. Cellular host factors interact with the viral RNA, influencing replication. An example is polypyrimidine tract binding protein (PTB), which binds to IRES. This bound initiates a cap independent translation of the virus, and has also been implicated in alternative splicing mechanisms.[4] Other factors within the host cell may alter the poliovirus replication cycle:
- Proteolytic processing of poliovirus proteins
- Lack of an host factor for viral replication
- Cease of protein synthesis within the host cell
Natural Reservoir
Only human cells, and certain primate species, show receptors for poliovirus. Therefore humans are considered the only natural reservoir for poliovirus.[5][6] The is no asymptomatic carrier state, except in the case of immunodeficient patients.[3]
References
- ↑ "Polyomavirus".
- ↑ "http://phil.cdc.gov/phil/details.asp". External link in
|title=(help) - ↑ 3.0 3.1 3.2 "Polyomavirus" (PDF).
- ↑ 4.0 4.1 4.2 4.3 4.4 4.5 4.6 4.7 4.8 Mueller S, Wimmer E, Cello J (2005). "Poliovirus and poliomyelitis: a tale of guts, brains, and an accidental event". Virus Res. 111 (2): 175–93. doi:10.1016/j.virusres.2005.04.008. PMID 15885840.
- ↑ Baury B, Masson D, McDermott BM, Jarry A, Blottière HM, Blanchardie P; et al. (2003). "Identification of secreted CD155 isoforms". Biochem Biophys Res Commun. 309 (1): 175–82. PMID 12943679.
- ↑ Belnap DM, McDermott BM, Filman DJ, Cheng N, Trus BL, Zuccola HJ; et al. (2000). "Three-dimensional structure of poliovirus receptor bound to poliovirus". Proc Natl Acad Sci U S A. 97 (1): 73–8. PMC 26618. PMID 10618373.