Polio causes: Difference between revisions

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{{Polio}}
{{CMG}}; {{AE}} {{JS}}


==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 [[serotype]]s 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 reservoir]]s for [[poliovirus]].
==Taxonomy==
[[Viruses]]; ssRNA viruses; ssRNA positive-strand viruses, no DNA stage; Picornavirales; [[Picornaviridae]]; [[Enterovirus]]; [[Poliovirus]]<ref name=NCBI>{{cite web | title = Polyomavirus | url = http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=138950 }}</ref>
==Biology==
{| style="float: right;"
| [[File:Polio EM PHIL 1875 lores.PNG|200px|thumb|none|A Transmission electron microscopy of poliovirus<SMALL> ''Image provided by the CDC [http://phil.cdc.gov/phil/details.asp Centers for Disease Control and Prevention] ''<ref>{{Cite web | title = http://phil.cdc.gov/phil/details.asp | url = http://phil.cdc.gov/phil/details.asp}}</ref></SMALL>]]
|}
[[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.<ref name=CDC>{{cite web | title = Polyomavirus | url = http://www.cdc.gov/vaccines/pubs/pinkbook/downloads/polio.pdf }}</ref><ref name="pmid15885840">{{cite journal| author=Mueller S, Wimmer E, Cello J| title=Poliovirus and poliomyelitis: a tale of guts, brains, and an accidental event. | journal=Virus Res | year= 2005 | volume= 111 | issue= 2 | pages= 175-93 | pmid=15885840 | doi=10.1016/j.virusres.2005.04.008 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15885840  }} </ref>  [[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 [[serotype]]s. 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.<ref name=CDC>{{cite web | title = Polyomavirus | url = http://www.cdc.gov/vaccines/pubs/pinkbook/downloads/polio.pdf }}</ref>
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.<ref name="pmid15885840">{{cite journal| author=Mueller S, Wimmer E, Cello J| title=Poliovirus and poliomyelitis: a tale of guts, brains, and an accidental event. | journal=Virus Res | year= 2005 | volume= 111 | issue= 2 | pages= 175-93 | pmid=15885840 | doi=10.1016/j.virusres.2005.04.008 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15885840  }} </ref>
==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.<ref name="pmid15885840">{{cite journal| author=Mueller S, Wimmer E, Cello J| title=Poliovirus and poliomyelitis: a tale of guts, brains, and an accidental event. | journal=Virus Res | year= 2005 | volume= 111 | issue= 2 | pages= 175-93 | pmid=15885840 | doi=10.1016/j.virusres.2005.04.008 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15885840  }} </ref>  At the 3' end of the genome is encoded a ''poly Adenine'' sequence, which varies about 60 adenylate residues in length.<ref name="pmid15885840">{{cite journal| author=Mueller S, Wimmer E, Cello J| title=Poliovirus and poliomyelitis: a tale of guts, brains, and an accidental event. | journal=Virus Res | year= 2005 | volume= 111 | issue= 2 | pages= 175-93 | pmid=15885840 | doi=10.1016/j.viruses.2005.04.008 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15885840  }} </ref>  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]].<ref name="pmid15885840">{{cite journal| author=Mueller S, Wimmer E, Cello J| title=Poliovirus and poliomyelitis: a tale of guts, brains, and an accidental event. | journal=Virus Res | year= 2005 | volume= 111 | issue= 2 | pages= 175-93 | pmid=15885840 | doi=10.1016/j.virusres.2005.04.008 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15885840  }} </ref>
==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:<ref name="pmid15885840">{{cite journal| author=Mueller S, Wimmer E, Cello J| title=Poliovirus and poliomyelitis: a tale of guts, brains, and an accidental event. | journal=Virus Res | year= 2005 | volume= 111 | issue= 2 | pages= 175-93 | pmid=15885840 | doi=10.1016/j.virusres.2005.04.008 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15885840  }} </ref>
* [[Brain]]
* [[Spinal cord]]
* [[Heart]]
* [[Skeletal muscle]]
* [[Leukocyte]]s
* [[Placenta]]
* [[Lung]]
* [[Ileum]]
* [[Liver]]
* [[Kidney]]
However, [[viral replication]] does not occur on all [[CD155]]-expressing cells.  Possible explanations include:<ref name="pmid15885840">{{cite journal| author=Mueller S, Wimmer E, Cello J| title=Poliovirus and poliomyelitis: a tale of guts, brains, and an accidental event. | journal=Virus Res | year= 2005 | volume= 111 | issue= 2 | pages= 175-93 | pmid=15885840 | doi=10.1016/j.virusres.2005.04.008 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15885840  }} </ref>
* 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 [[viral replication|replication]].
CD155 positive tissues involved in the [[pathogenesis]] of the [[virus]], include:<ref name="pmid15885840">{{cite journal| author=Mueller S, Wimmer E, Cello J| title=Poliovirus and poliomyelitis: a tale of guts, brains, and an accidental event. | journal=Virus Res | year= 2005 | volume= 111 | issue= 2 | pages= 175-93 | pmid=15885840 | doi=10.1016/j.virusres.2005.04.008 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15885840  }} </ref>
* 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.<ref name="pmid15885840">{{cite journal| author=Mueller S, Wimmer E, Cello J| title=Poliovirus and poliomyelitis: a tale of guts, brains, and an accidental event. | journal=Virus Res | year= 2005 | volume= 111 | issue= 2 | pages= 175-93 | pmid=15885840 | doi=10.1016/j.virusres.2005.04.008 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15885840  }} </ref>  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]].<ref name="pmid12943679">{{cite journal| author=Baury B, Masson D, McDermott BM, Jarry A, Blottière HM, Blanchardie P et al.| title=Identification of secreted CD155 isoforms. | journal=Biochem Biophys Res Commun | year= 2003 | volume= 309 | issue= 1 | pages= 175-82 | pmid=12943679 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12943679  }} </ref><ref name="pmid10618373">{{cite journal| author=Belnap DM, McDermott BM, Filman DJ, Cheng N, Trus BL, Zuccola HJ et al.| title=Three-dimensional structure of poliovirus receptor bound to poliovirus. | journal=Proc Natl Acad Sci U S A | year= 2000 | volume= 97 | issue= 1 | pages= 73-8 | pmid=10618373 | doi= | pmc=PMC26618 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10618373  }} </ref>
==References==
{{Reflist|2}}
[[Category:Disease]]
[[Category:Infectious disease]]
[[Category:Primary care]]
{{WH}}
{{WS}}

Latest revision as of 19:17, 29 August 2014