Poliovirus: Difference between revisions

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==Overview==
==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]].
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 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 reservoir]]s for [[poliovirus]].


==Taxonomy==
==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>
[[Viruses]]; ssRNA viruses; ssRNA positive-strand viruses, no DNA stage; Picornavirales; [[Picornaviridae]]; [[Enterovirus]]; [[Poliovirus]]<ref name=NCBI>{{cite web | title = Poliovirus | url = http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=138950 }}</ref>


==Biology==
==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.<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.
[[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> 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 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>
There are three [[serotype]]s of poliovirus (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 any of the other [[serotype]]s. 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, namely: 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>
 
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==
==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>
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 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==
==Tropism==
===Extra-Cellular Tissue Tropism===
===Extracellular Factors===
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>
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]]
* [[Brain]]
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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>
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.
* 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 the [[virus]].
* Excess [[secretion]] of non-receptor isoforms of [[CD155]] may compete for the virus, thereby inactivating it.
* Other ligands may compete with [[poliovirus]] for [[CD155]].
* Other ligands may compete with [[poliovirus]] for [[CD155]].
* Physical barriers may block [[poliovirus]] access to [[CD155]].
* Physical barriers may block [[poliovirus]] access to [[CD155]].
* [[Cytoplasm]] of certain cells may be inadequate for poliovirus [[viral replication|replication]].
* [[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>
[[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 [[tonsils]]
* Germinal centers of [[Peyer's patches]]
* Germinal centers of [[Peyer's patches]]
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* [[Colon]] [[enterocytes]]
* [[Colon]] [[enterocytes]]


===Intra-Cellular Tissue Tropism===
===Intracellular Factors===
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:
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.<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
* Proteolytic processing of poliovirus proteins
* Lack of an host factor for viral replication
* Lack of an host factors for viral replication
* Cease of protein synthesis within the host cell
* Cessation of protein synthesis within the host cell


==Natural Reservoir==
==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>  The is no [[asymptomatic]] carrier state, except in the case of immunodeficient patients.<ref name=CDC>{{cite web | title = Polyomavirus | url = http://www.cdc.gov/vaccines/pubs/pinkbook/downloads/polio.pdf }}</ref>
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>  There is no [[asymptomatic]] carrier state, except in the case of immunodeficient patients.<ref name=CDC>{{cite web | title = Polyomavirus | url = http://www.cdc.gov/vaccines/pubs/pinkbook/downloads/polio.pdf }}</ref>


==References==
==References==
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{{Reflist|2}}
[[Category:Disease]]
[[Category:Infectious disease]]
[[Category:Primary care]]
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This polypeptide is then cleaved into approximately 10 individual viral proteins, including:<ref name = Goodsell /><ref name= Chan/>
[[Image:Poliovirus genome.png|thumb|left|300px|The genomic structure of poliovirus type 1<ref name=DeJesus/> (see text or reference for further details).]]
 
*''3D<sup>pol</sup>'', an [[RNA dependent RNA polymerase]]. 
*''2A<sup>pro</sup>'' and ''3C<sup>pro</sup>/3CD<sup>pro</sup>'', [[protease]]s which cleave the viral polypeptide.
*''[[VPg]]'' (3B), a small protein that binds viral RNA and is necessary for synthesis of viral positive and negative strand RNA.
*''2BC, 2B, 2C, 3AB, 3A, 3B'' proteins which comprise the protein complex needed for virus replication.
*''VP0, VP1, VP2, VP3, VP4'' proteins of the viral capsid.
 
 
== Immune system avoidance ==
 
Poliovirus uses two key mechanisms to evade the [[immune system]]. First, it is capable of surviving the highly [[pH|acidic]] conditions of the [[gastrointestinal tract]], allowing the virus to infect the host and spread throughout the body via the [[lymphatic system]].<ref name= Goodsell/>  Second, because it can replicate very rapidly - the virus overwhelms the host organs before an immune response can be mounted.<ref name= Racaniello>{{cite journal |author=Racaniello V |title=One hundred years of poliovirus pathogenesis |journal=Virology |volume=344 |issue=1 |pages=9-16 |year=2006 |pmid = 16364730}}</ref>
 
Individuals who are exposed to poliovirus, either through infection or by [[immunization]] with [[polio vaccine]], develop [[immunity (medical)|immunity]].  In immune individuals, [[antibodies]] against poliovirus are present in the [[tonsil]]s 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.<ref name=Kew_2005/> Infection with one serotype of poliovirus does not provide immunity against the other serotypes, however second attacks within the same individual are extremely rare.
 
== PVR transgenic mouse ==
 
Although humans are the only known natural hosts of poliovirus, monkeys can be experimentally infected and they have long been used to study poliovirus. In 1990-91, a small animal model of poliomyelitis was developed by two laboratories.  Mice were [[Genetic engineering|engineered]] to express a human receptor to poliovirus (hPVR).<ref name="pmid2170026">{{cite journal |author=Ren RB, Costantini F, Gorgacz EJ, Lee JJ, Racaniello VR |title=Transgenic mice expressing a human poliovirus receptor: a new model for poliomyelitis |journal=Cell |volume=63 |issue=2 |pages=353-62 |year=1990 |pmid=2170026 |doi=}}</ref><ref name="pmid1846972">{{cite journal |author=Koike S, Taya C, Kurata T, ''et al'' |title=Transgenic mice susceptible to poliovirus |url= http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=1846972 |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=88 |issue=3 |pages=951-5 |year=1991 |pmid=1846972 |doi=}}</ref>
 
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]].<ref name="pmid8289371">{{cite journal |author=Horie H, Koike S, Kurata T, ''et al'' |title=Transgenic mice carrying the human poliovirus receptor: new animal models for study of poliovirus neurovirulence | url= http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=8289371| journal=J. Virol. |volume=68 |issue=2 |pages=681-8 |year=1994 |pmid=8289371 |doi=}}</ref> 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 [[Histopathology|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.<ref name="pmid11597452">{{cite journal |author=Ohka S, Nomoto A |title=Recent insights into poliovirus pathogenesis |journal=Trends Microbiol. |volume=9 |issue=10 |pages=501-6 |year=2001 |pmid=11597452 |doi=}}</ref> 
 
Three distinct types of TgPVR mice have been well studied:<ref name="pmid7832641">{{cite journal |author=Koike S, Taya C, Aoki J, ''et al'' |title=Characterization of three different transgenic mouse lines that carry human poliovirus receptor gene--influence of the transgene expression on pathogenesis |journal=Arch. Virol. |volume=139 |issue=3-4 |pages=351-63 |year=1994 |pmid=7832641 |doi=}}</ref>
 
*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 [[mucosa]]l infection model.<ref name="pmid15033568">{{cite journal |author=Nagata N, Iwasaki T, Ami Y, ''et al'' |title=A poliomyelitis model through mucosal infection in transgenic mice bearing human poliovirus receptor, TgPVR21 |journal=Virology |volume=321 |issue=1 |pages=87-100 |year=2004 |pmid=15033568 |doi=10.1016/j.virol.2003.12.008}}</ref>
*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 [[Poliomyelitis#Bulbar polio|bulbar form of polio]] after intranasal inoculation.<ref name="pmid15033568"/>
 
The development of the TgPVR mouse has had a profound effect on oral [[poliovirus vaccine]] (OPV) production. Previously, monitoring the safety of OPV had to be performed using monkeys, because only primates are susceptible to the virus. In 1999 the [[World Health Organization]] approved the use of the TgPVR mouse as an alternative method of assessing the effectiveness of the vaccine against poliovirus type-3. In 2000 the mouse model was approved for tests of vaccines against type-1 and type-2 poliovirus.<ref name="pmid12764491">{{cite journal |author=Dragunsky E, Nomura T, Karpinski K, ''et al'' |title=Transgenic mice as an alternative to monkeys for neurovirulence testing of live oral poliovirus vaccine: validation by a WHO collaborative study |url= http://www.scielosp.org/scielo.php?script=sci_arttext&pid=S0042-96862003000400006&lng=en&nrm=iso&tlng=en |journal=Bull. World Health Organ. |volume=81 |issue=4 |pages=251-60 |year=2003 |pmid=12764491 |doi=}}</ref>
 
== Cloning and synthesis ==
 
[[Image:Polyovirus.jpg|thumb|left|The structural appearance of Poliovirus.]]
 
In 1981 Racaniello and Baltimore used recombinant DNA technology to generate the first infectious [[Molecular cloning|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.<ref>{{cite journal |author=Racaniello V, Baltimore D |title=Cloned poliovirus complemenatry DNA is infectious in mammalian cells |journal=Science |volume=214 |issue=453 |pages=916-919 |year=1981 |pmid=6272391}}</ref> 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.<ref>{{cite journal |author=Cello J, Paul AV, Wimmer E |title=Chemical synthesis of poliovirus cDNA: generation of infectious virus in the absence of natural template |journal=Science |volume=297 |issue=5583 |pages=1016-8 |year=2002 |pmid=12114528 |doi=10.1126/science.1072266}}</ref> Using the published [[genetic code]], the scientists first converted poliovirus's RNA sequence into a DNA sequence, and short fragments of the DNA sequence were assembled. The complete virus was then assembled by a [[gene synthesis]] company. Nineteen [[Marker gene|markers]] were incorporated into the synthesized DNA, so that it could be distinguished from natural poliovirus. [[Enzyme]]s were used to convert the DNA back into RNA, its natural state. 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.<ref>{{cite journal |author=Couzin J |title=Virology. Active poliovirus baked from scratch |journal=Science |volume=297 |issue=5579 |pages=174-5 |year=2002 |pmid=12114601 |doi=10.1126/science.297.5579.174b}}</ref>
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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 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.

Taxonomy

Viruses; ssRNA viruses; ssRNA positive-strand viruses, no DNA stage; Picornavirales; Picornaviridae; Enterovirus; Poliovirus[1]

Biology

A Transmission electron microscopy of poliovirus Image provided by the CDC Centers for Disease Control and Prevention [2]

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] 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.[3] 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.[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 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

Extracellular Factors

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 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.

CD155 positive tissues involved in the pathogenesis of the virus, include:[4]

Intracellular Factors

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.[4] 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

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] There is no asymptomatic carrier state, except in the case of immunodeficient patients.[3]

References

  1. "Poliovirus".
  2. "http://phil.cdc.gov/phil/details.asp". External link in |title= (help)
  3. 3.0 3.1 3.2 "Polyomavirus" (PDF).
  4. 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.
  5. 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.
  6. 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.

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