View source for Poliovirus

{{Short description|Enterovirus}}
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{{Good article}}
{{Virusbox
| image = Polio.jpg
| image_alt = TEM micrograph of poliovirus virions. Scale bar, 50 nm.
| image_caption = [[Transmission electron microscopy|TEM]] [[micrograph]] of poliovirus [[Virus#Structure|virions]]. Scale bar (white): 50&nbsp;nm
| image2 = Polio-3-chains.png
| image2_alt = A type 3 poliovirus capsid coloured by chains
| image2_caption = A type 3 poliovirus capsid, protein side chains coloured
| parent = Enterovirus 
| species = Enterovirus C
| virus = Poliovirus
| subdivision_ranks = Serotypes
| subdivision = *''PV-1'' (''[[Poliovirus-1]]'')
*''PV-2'' (''[[Poliovirus-2]]'')
*''PV-3'' (''[[Poliovirus-3]]'')
}}
'''Poliovirus''', the causative agent of [[polio]] (also known as poliomyelitis), is a serotype of the species ''[[Enterovirus C]]'', in the family of ''[[Picornaviridae]]''.<ref name="Sherris">{{cite book |veditors=Ryan KJ, Ray CG | title = Sherris Medical Microbiology | edition = 4th | publisher = McGraw Hill | year = 2004 | isbn = 978-0-8385-8529-0|page= }}{{page needed|date=August 2021}}</ref>  There are [[#Origin and serotypes|three poliovirus serotypes]], numbered 1, 2, and 3.

Poliovirus is composed of an [[RNA]] [[genome]] and a [[protein]] [[capsid]]. The genome is a [[Positive-sense single-stranded RNA virus|single-stranded positive-sense RNA]] (+ssRNA) genome that is about 7500 [[nucleotide]]s long.<ref name="Hogle">{{cite journal | vauthors = Hogle JM | title = Poliovirus cell entry: common structural themes in viral cell entry pathways | journal = Annual Review of Microbiology | volume = 56 | pages = 677–702 | year = 2002 | pmid = 12142481 | pmc = 1500891 | doi = 10.1146/annurev.micro.56.012302.160757 }}</ref> The viral particle is about 30 [[nanometre|nm]] in diameter with [[icosahedral symmetry]]. Because of its short genome and its simple composition—only a strand of RNA and a [[viral envelope|nonenveloped]] icosahedral protein coat [[capsid|encapsulating]] it—poliovirus is widely regarded as the simplest significant virus.<ref name="Goodsell">{{cite book | vauthors = Goodsell DS |title=The machinery of life |publisher=Copernicus |location=New York |year=1998 |isbn=978-0-387-98273-1 |page=}}{{page needed|date=August 2021}}</ref>

Poliovirus is one of the most well-characterized viruses, and has become a useful model system for understanding the biology of [[RNA viruses]].

== Replication cycle ==
[[Image:Poliovirus life cycle.png|thumb|upright=1.5|right|The replication cycle of poliovirus is initiated by binding to the cell surface receptor CD155 (1). The virion forms a pore in the cell membrane through which viral RNA is released into the cytoplasm (2). Translation of the viral RNA occurs by an IRES-mediated mechanism (3). The polyprotein is cleaved, yielding mature viral proteins (4). The positive-sense RNA serves as template for complementary negative-strand synthesis, producing double-stranded replicative form (RF) RNA (5). Many positive strand RNA copies are produced from the single negative strand (6). The newly synthesized positive-sense RNA molecules can serve as templates for translation of more viral proteins (7) or can be enclosed in a capsid (8), which ultimately generates progeny virions. Lysis of the infected cell results in release of infectious progeny virions (9).<ref name="DeJesus">{{cite journal | vauthors = De Jesus NH | title = Epidemics to eradication: the modern history of poliomyelitis | journal = Virology Journal | volume = 4 | issue = 1 | pages = 70 | date = July 2007 | pmid = 17623069 | pmc = 1947962 | doi = 10.1186/1743-422X-4-70 | doi-access = free }}</ref>]]

Poliovirus infects human cells by binding to an [[immunoglobulin]]-like receptor, [[CD155]] (also known as the poliovirus receptor or PVR)<ref name="Mendelsohn">{{cite journal | vauthors = Mendelsohn CL, Wimmer E, Racaniello VR | title = Cellular receptor for poliovirus: molecular cloning, nucleotide sequence, and expression of a new member of the immunoglobulin superfamily | journal = Cell | volume = 56 | issue = 5 | pages = 855–865 | date = March 1989 | pmid = 2538245 | doi = 10.1016/0092-8674(89)90690-9 | s2cid = 44296539 }}</ref><ref name="He">{{cite journal | vauthors = He Y, Mueller S, Chipman PR, Bator CM, Peng X, Bowman VD, Mukhopadhyay S, Wimmer E, Kuhn RJ, Rossmann MG | title = Complexes of poliovirus serotypes with their common cellular receptor, CD155 | journal = Journal of Virology | volume = 77 | issue = 8 | pages = 4827–4835 | date = April 2003 | pmid = 12663789 | pmc = 152153 | doi = 10.1128/JVI.77.8.4827-4835.2003 }}</ref> on the cell surface.<ref name="Dunnebacke">{{cite journal | vauthors = Dunnebacke TH, Levinthal JD, Williams RC | title = Entry and release of poliovirus as observed by electron microscopy of cultured cells | journal = Journal of Virology | volume = 4 | issue = 4 | pages = 505–513 | date = October 1969 | pmid = 4309884 | pmc = 375900 | doi = 10.1128/JVI.4.4.505-513.1969 }}</ref> Interaction of poliovirus and CD155 facilitates an irreversible conformational change of the viral particle necessary for viral entry.<ref name="Kaplan">{{cite journal | vauthors = Kaplan G, Freistadt MS, Racaniello VR | title = Neutralization of poliovirus by cell receptors expressed in insect cells | journal = Journal of Virology | volume = 64 | issue = 10 | pages = 4697–4702 | date = October 1990 | pmid = 2168959 | pmc = 247955 | doi = 10.1128/JVI.64.10.4697-4702.1990 }}</ref><ref name="Gomez">{{cite journal | vauthors = Gómez Yafal A, Kaplan G, Racaniello VR, Hogle JM | title = Characterization of poliovirus conformational alteration mediated by soluble cell receptors | journal = Virology | volume = 197 | issue = 1 | pages = 501–505 | date = November 1993 | pmid = 8212594 | doi = 10.1006/viro.1993.1621 }}</ref> Following attachment to the host [[cell membrane]], entry of the viral nucleic acid was thought to occur one of two ways: via the formation of a [[Aquaporin|pore]] in the plasma membrane through which the RNA is then "injected" into the host cell [[cytoplasm]], or via virus uptake by [[receptor-mediated endocytosis]].<ref name="Mueller">{{cite journal | vauthors = Mueller S, Wimmer E, Cello J | title = Poliovirus and poliomyelitis: a tale of guts, brains, and an accidental event | journal = Virus Research | volume = 111 | issue = 2 | pages = 175–193 | date = August 2005 | pmid = 15885840 | doi = 10.1016/j.virusres.2005.04.008 }}</ref> Recent experimental evidence supports the latter hypothesis and suggests that poliovirus binds to CD155 and is taken up by endocytosis. Immediately after internalization of the particle, the viral RNA is released.<ref name="Brandenburg">{{cite journal | vauthors = Brandenburg B, Lee LY, Lakadamyali M, Rust MJ, Zhuang X, Hogle JM | title = Imaging poliovirus entry in live cells | journal = PLOS Biology | volume = 5 | issue = 7 | pages = e183 | date = July 2007 | pmid = 17622193 | pmc = 1914398 | doi = 10.1371/journal.pbio.0050183 | doi-access = free }}</ref>

Poliovirus is a positive-stranded [[RNA virus]]. Thus, the genome enclosed within the viral particle can be used as [[messenger RNA]] and immediately [[translation (biology)|translated]] by the host cell. On entry, the virus hijacks the cell's translation machinery, causing inhibition of cellular protein synthesis in favor of virus-specific protein production.<ref name="pmid13965389">{{cite journal | vauthors = Attardi G, Smith J | title = Virus specific protein and a ribo-nucleic acid associated with ribosomes in poliovirus infected HeLa cells | journal = Cold Spring Harbor Symposia on Quantitative Biology | volume = 27 | pages = 271–292 | date = 1962 | pmid = 13965389 | doi = 10.1101/SQB.1962.027.001.026 }}</ref> Unlike the host cell's mRNAs, the [[Five prime untranslated region|5'&nbsp;end]] of poliovirus RNA is extremely long—over 700 nucleotides—and highly structured. This region of the viral genome is called an [[internal ribosome entry site]] (IRES). This region consists of many secondary structures and 3 or 4 domains. Domain 3 is a self folding RNA element that contains conserved structural motifs in various stable stem loops linked by two four-way junctions. As IRES consists of many domains, these domains themselves consist of many loops that contribute to modified translation without a 5’ end cap by hijacking ribosomes. The interaction loop of domain 3 is known as GNRA tetraloop. The residues of adenosines A180 and A181 in the GUAA tetraloop form hydrogen bonds via non canonical base pairing interactions with the base pairs of the receptors C230/G242 and G231/C241, respectively.<ref>{{cite journal | vauthors = Lozano G, Fernandez N, Martinez-Salas E | title = Modeling Three-Dimensional Structural Motifs of Viral IRES | journal = Journal of Molecular Biology | volume = 428 | issue = 5 Pt A | pages = 767–776 | date = February 2016 | pmid = 26778619 | doi = 10.1016/j.jmb.2016.01.005 }}</ref> Genetic mutations in this region prevent viral protein production.<ref name="Chen">{{cite journal | vauthors = Chen CY, Sarnow P | title = Initiation of protein synthesis by the eukaryotic translational apparatus on circular RNAs | journal = Science | volume = 268 | issue = 5209 | pages = 415–417 | date = April 1995 | pmid = 7536344 | doi = 10.1126/science.7536344 | bibcode = 1995Sci...268..415C }}</ref><ref name="Pelletier">{{cite journal | vauthors = Pelletier J, Sonenberg N | title = Internal initiation of translation of eukaryotic mRNA directed by a sequence derived from poliovirus RNA | journal = Nature | volume = 334 | issue = 6180 | pages = 320–325 | date = July 1988 | pmid = 2839775 | doi = 10.1038/334320a0 | s2cid = 4327857 | bibcode = 1988Natur.334..320P }}</ref><ref name="Jang">{{cite journal | vauthors = Jang SK, Kräusslich HG, Nicklin MJ, Duke GM, Palmenberg AC, Wimmer E | title = A segment of the 5' nontranslated region of encephalomyocarditis virus RNA directs internal entry of ribosomes during in vitro translation | journal = Journal of Virology | volume = 62 | issue = 8 | pages = 2636–2643 | date = August 1988 | pmid = 2839690 | pmc = 253694 | doi = 10.1128/JVI.62.8.2636-2643.1988 }}</ref> The first IRES to be discovered was found in poliovirus RNA.<ref>{{cite book| vauthors = Carter J, Saunders VA | chapter = Viruses and their importance |title=Virology: Principles and Applications|chapter-url=https://books.google.com/books?id=EKRgZCdr-74C&pg=PA4|year=2007|publisher=John Wiley & Sons|isbn=978-0-470-02386-0|page=4}}</ref>

Poliovirus mRNA is translated as one long [[polypeptide]]. This polypeptide is then autocleaved by internal proteases into about 10 individual viral proteins. Not all cleavages occur with the same efficiency. Therefore, the amounts of proteins produced by the polypeptide cleavage vary: for example, smaller amounts of 3D<sup>pol</sup> are produced than those of capsid proteins, VP1–4.<ref name="Carter_2007" />{{rp|165}}<ref>{{Cite book|title=Viruses: Biology, Applications, and Control | vauthors = Harper DR |publisher=Garland Science|year=2012|isbn=978-0-8153-4150-5|location=The United States of America|page=}}{{page needed|date=August 2021}}</ref> These individual viral proteins are:<ref name = Goodsell /><ref>{{cite web|title=Poliomyelitis|publisher=Brown University|url= http://www.brown.edu/Courses/Bio_160/Projects2000/Polio/TableofContents.html|url-status=dead|archive-url= https://web.archive.org/web/20070222133944/http://www.brown.edu/Courses/Bio_160/Projects2000/Polio/TableofContents.html|archive-date=February 22, 2007}}</ref>
[[Image:Poliovirus genome.png|thumb|right|upright=1.5|The genomic structure of poliovirus type 1<ref name=DeJesus/>]]
*3D<sup>pol</sup>, an [[RNA dependent RNA polymerase]] whose function is to make multiple copies of the viral RNA genome
*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 (an ATPase)<ref>{{cite book| vauthors = Carter J, Saunders VA | chapter = Picornavirus replication |title=Virology: Principles and Applications| chapter-url=https://books.google.com/books?id=EKRgZCdr-74C&pg=PA164|date=2007|publisher=John Wiley & Sons|isbn=978-0-470-02386-0|page=164}}</ref>'', 3AB, 3A, 3B'' proteins which comprise the protein complex needed for virus replication.
*VP0, which is further cleaved into VP2 and VP4, VP1 and VP3, proteins of the viral capsid

After translation, transcription and genome replication which involve a single process, synthesis of (+) RNA) is realized. For the infecting (+)RNA to be replicated, multiple copies of (−)RNA must be transcribed and then used as templates for (+)RNA synthesis. Replicative intermediates (RIs), which are an association of RNA molecules consisting of a template RNA and several growing RNAs of varying length, are seen in both the replication complexes for (−)RNAs and (+)RNAs. For synthesis of each negative-strand and positive-strand RNAs, VPg protein in the poliovirus works as a primer. RNA-dependent RNA polymerase of the poliovirus adds two uracil nucleotides (UU) to VPg protein utilizing the poly(A) tail at the 3′-end of the +ssRNA genome as a pattern for synthesis of the negative-strand antigenomic RNA. To initiate this −ssRNA synthesis, the tyrosine hydroxyl of VPg is needed. But for the initiation of positive strand RNA synthesis, CRE-dependent VPg uridylylation is needed. Which means that VPg is once more utilized as a primer however this time it adds the two uridine triphosphates using a cis-acting replication element (CRE) as a template.<ref>{{cite book | vauthors = Louten J |chapter =Poliovirus |date=2016 |title =Essential Human Virology|pages=257–71|publisher=Elsevier |doi=10.1016/b978-0-12-800947-5.00014-4|isbn=978-0-12-800947-5}}</ref><ref>{{cite journal | vauthors = Murray KE, Barton DJ | title = Poliovirus CRE-dependent VPg uridylylation is required for positive-strand RNA synthesis but not for negative-strand RNA synthesis | journal = Journal of Virology | volume = 77 | issue = 8 | pages = 4739–4750 | date = April 2003 | pmid = 12663781 | pmc = 152113 | doi = 10.1128/JVI.77.8.4739-4750.2003 }}</ref> <!-- (cre) -->

The CRE of poliovirus is identified as an unachieved base-paired stem and a final loop consisting of 61 nt. The CRE is found in enteroviruses. It is a highly preserved secondary RNA structural element and bedded in the genome's polyprotein-coding region. The complex can be translocated to the 5'  region of the genome that have no coding activity, at least 3.7-kb distant from the initial location. This process can occurs without negatively influencing activity. CRE copies do not influence replication negatively. Uridylylation process of VPg that takes place at CRE needs the presence of 3CD<sup>pro</sup> that is an RNA binding protein. It is attached to the CRE directly and specifically. Because of its presence VPg can bind the CRE properly and primary production proceeds without problems.<ref>{{cite journal | vauthors = Goodfellow IG, Kerrigan D, Evans DJ | title = Structure and function analysis of the poliovirus cis-acting replication element (CRE) | journal = RNA | volume = 9 | issue = 1 | pages = 124–137 | date = January 2003 | pmid = 12554882 | pmc = 1370376 | doi = 10.1261/rna.2950603 }}</ref>

Some of the (+) RNA molecules are used as templates for further (−) RNA synthesis, some function as mRNA, and some are destined to be the genomes of progeny virions.<ref name="Carter_2007" />

In the assembly of new virus particles (i.e. the packaging of progeny genome into a procapsid which can survive outside the host cell), including, respectively:<ref name = "Carter_2007">{{cite book| vauthors = Carter J, Saunders VA | chapter = Picornavirus replication |title=Virology: Principles and Applications| chapter-url=https://books.google.com/books?id=EKRgZCdr-74C&pg=PA165|date=2007|publisher=John Wiley & Sons|isbn=978-0-470-02386-0|pages=161–169|access-date=2016-10-19|archive-date=2023-01-14|archive-url=https://web.archive.org/web/20230114012046/https://books.google.com/books?id=EKRgZCdr-74C&pg=PA165|url-status=live}}</ref>{{rp|161,165}}
* Five copies each of VP0, VP3, and VP1 whose N termini and VP4 form interior surface of capsid, assemble into a 'pentamer' and 12 pentamers form a procapsid. (The outer surface of capsid is consisting of VP1, VP2, VP3; C termini of VP1 and VP3 form the canyons which around each of the vertices; around this time, the 60 copies of VP0 are cleaved into VP4 and VP2.)
* Each procapsid acquires a copy of the virus genome, with VPg still attached at the 5' end.

Fully assembled poliovirus leaves the confines of its host cell by [[lysis]]<ref>{{cite book| vauthors = Carter J, Saunders VA | chapter = Picornavirus replication |title=Virology: Principles and Applications| chapter-url=https://books.google.com/books?id=EKRgZCdr-74C&pg=PA166|date=2007|publisher=John Wiley & Sons|isbn=978-0-470-02386-0|page=166}}</ref> 4 to 6 hours following initiation of infection in cultured mammalian cells.<ref name="Kew_2005">{{cite journal | vauthors = Kew OM, Sutter RW, de Gourville EM, Dowdle WR, Pallansch MA | title = Vaccine-derived polioviruses and the endgame strategy for global polio eradication | journal = Annual Review of Microbiology | volume = 59 | pages = 587–635 | year = 2005 | pmid = 16153180 | doi = 10.1146/annurev.micro.58.030603.123625 | url = https://zenodo.org/record/1235033 | access-date = 2018-10-26 | url-status = live | archive-url = https://web.archive.org/web/20200709053801/https://zenodo.org/record/1235033 | archive-date = 2020-07-09 }}</ref> The mechanism of viral release from the cell is unclear,<ref name="Hogle" /> but each dying cell can release up to 10,000 polio [[virions]].<ref name="Kew_2005" />

Drake demonstrated that poliovirus is able to undergo multiplicity reactivation.<ref>{{cite journal | vauthors = Drake JW | title = Interference and multiplicity reactivation in polioviruses | journal = Virology | volume = 6 | issue = 1 | pages = 244–264 | date = August 1958 | pmid = 13581529 | doi = 10.1016/0042-6822(58)90073-4 }}</ref>  That is, when polioviruses were irradiated with UV light and allowed to undergo multiple infections of host cells, viable progeny could be formed even at UV doses that inactivated the virus in single infections. Poliovirus can undergo [[genetic recombination]] when at least two viral [[genome]]s are present in the same host cell.  Kirkegaard and Baltimore<ref>{{cite journal | vauthors = Kirkegaard K, Baltimore D | title = The mechanism of RNA recombination in poliovirus | journal = Cell | volume = 47 | issue = 3 | pages = 433–443 | date = November 1986 | pmid = 3021340 | pmc = 7133339 | doi = 10.1016/0092-8674(86)90600-8 }}</ref> presented evidence that [[RNA-dependent RNA polymerase]] (RdRP) catalyzes recombination by a copy choice mechanism in which the RdRP switches between [[positive-sense single-stranded RNA virus|(+)ssRNA]] templates during negative strand synthesis.  Recombination in RNA viruses appears to be an adaptive mechanism for repairing genome damage.<ref>{{cite journal | vauthors = Barr JN, Fearns R | title = How RNA viruses maintain their genome integrity | journal = The Journal of General Virology | volume = 91 | issue = Pt 6 | pages = 1373–1387 | date = June 2010 | pmid = 20335491 | doi = 10.1099/vir.0.020818-0 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Bernstein H, Bernstein C, Michod RE | title = Sex in microbial pathogens | journal = Infection, Genetics and Evolution | volume = 57 | pages = 8–25 | date = January 2018 | pmid = 29111273 | doi = 10.1016/j.meegid.2017.10.024 | doi-access = free | bibcode = 2018InfGE..57....8B }}</ref>

== Origin and serotypes ==
Poliovirus is structurally similar to other human enteroviruses ([[coxsackievirus]]es, [[echovirus]]es, and [[rhinovirus]]es), which also use immunoglobulin-like molecules to recognize and enter host cells.<ref name=He/> [[Phylogenetic]] analysis of the RNA and protein sequences of poliovirus  suggests that it may have evolved from a C-cluster [[Coxsackie A virus]] [[common descent|ancestor]] through a mutation in the capsid.<ref>{{cite journal | vauthors = Jiang P, Faase JA, Toyoda H, Paul A, Wimmer E, Gorbalenya AE | title = Evidence for emergence of diverse polioviruses from C-cluster coxsackie A viruses and implications for global poliovirus eradication | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 104 | issue = 22 | pages = 9457–9462 | date = May 2007 | pmid = 17517601 | pmc = 1874223 | doi = 10.1073/pnas.0700451104 | doi-access = free | bibcode = 2007PNAS..104.9457J }}</ref> The distinct [[speciation]] of poliovirus probably occurred as a result of a change in cellular receptor specificity from [[intercellular adhesion molecule-1]] (ICAM-1) (used by C-cluster Coxsackie A viruses) to [[CD155]], leading to a change in pathogenicity and allowing the virus to infect nerve tissue.

The mutation rate in the virus is relatively high even for an RNA virus, with a synonymous substitution rate of {{nowrap|1.0 × 10<sup>−2</sup>}} substitutions/site/year and a
non-synonymous substitution rate of {{nowrap|3.0 × 10<sup>−4</sup>}} substitutions/site/year.<ref>{{cite journal | vauthors = Jorba J, Campagnoli R, De L, Kew O | title = Calibration of multiple poliovirus molecular clocks covering an extended evolutionary range | journal = Journal of Virology | volume = 82 | issue = 9 | pages = 4429–4440 | date = May 2008 | pmid = 18287242 | pmc = 2293050 | doi = 10.1128/JVI.02354-07 }}</ref> Base distribution within the genome is not random; [[adenosine]] is less common than expected at the 5' end and higher at the 3' end.<ref name="Rothberg1981">{{cite journal | vauthors = Rothberg PG, Wimmer E | title = Mononucleotide and dinucleotide frequencies, and codon usage in poliovirion RNA | journal = Nucleic Acids Research | volume = 9 | issue = 23 | pages = 6221–6229 | date = December 1981 | pmid = 6275352 | pmc = 327599 | doi = 10.1093/nar/9.23.6221 }}</ref> [[Codon]] use is not random; codons ending in adenosine are favoured, and those ending in [[cytosine]] or [[guanine]] are avoided. Codon use differs between the three genotypes, and appears to be driven by mutation rather than selection.<ref name="Zhang2011">{{cite journal | vauthors = Zhang J, Wang M, Liu WQ, Zhou JH, Chen HT, Ma LN, Ding YZ, Gu YX, Liu YS | title = Analysis of codon usage and nucleotide composition bias in polioviruses | journal = Virology Journal | volume = 8 | pages = 146 | date = March 2011 | pmid = 21450075 | pmc = 3079669 | doi = 10.1186/1743-422X-8-146 | doi-access = free }}</ref>

The three [[serotype]]s of poliovirus, PV-1, PV-2, and PV-3, each have a slightly different [[capsid]] protein. Capsid proteins define cellular receptor specificity and virus antigenicity. ''PV-1'' is the most common form encountered in nature, but all three forms are extremely [[infectious disease|infectious]].<ref name=Paul_1971/> As of March 2020, wild PV-1 is highly localized to regions in Pakistan and Afghanistan. Certification of the eradication of indigenous transmission of wild PV-2 occurred in September 2015, after last being detected in 1999,<ref name="Global eradication of wild poliovirus type 2 declared">{{cite web |url=http://www.polioeradication.org/mediaroom/newsstories/Global-eradication-of-wild-poliovirus-type-2-declared/tabid/526/news/1289/Default.aspx |title=Global eradication of wild poliovirus type 2 declared |publisher=[[Global Polio Eradication Initiative]] |date=2015-09-20 |access-date=2015-09-30 |archive-date=2015-09-28 |archive-url=https://web.archive.org/web/20150928215451/http://www.polioeradication.org/mediaroom/newsstories/Global-eradication-of-wild-poliovirus-type-2-declared/tabid/526/news/1289/Default.aspx |url-status=live }}</ref> and in October 2019 for wild PV-3 after last being detected in 2012.<ref name="polioeradication.org">{{Cite web|url=http://polioeradication.org/news-post/two-out-of-three-wild-poliovirus-strains-eradicated/|title=GPEI-Two out of three wild poliovirus strains eradicated|language=en-GB|access-date=2019-11-02|archive-date=2019-11-07|archive-url=https://web.archive.org/web/20191107080405/http://polioeradication.org/news-post/two-out-of-three-wild-poliovirus-strains-eradicated/|url-status=live}}</ref> However, circulating vaccine-derived poliovirus (variant poliovirus, cVDPV) of all three serotypes continues to circulate and cause paralysis, having been detected in 32 countries in 2023.<ref>{{cite journal | vauthors = Geiger K, Stehling-Ariza T, Bigouette JP, Bennett SD, Burns CC, Quddus A, Wassilak SG, Bolu O | title = Progress Toward Poliomyelitis Eradication - Worldwide, January 2022-December 2023 | language = en-us | journal = MMWR. Morbidity and Mortality Weekly Report | volume = 73 | issue = 19 | pages = 441–446 | date = May 2024 | pmid = 38753550 | doi = 10.15585/mmwr.mm7319a4 | pmc = 11115430 }}</ref>

Specific strains of each serotype are used to prepare [[polio vaccine|vaccines against polio]]. Inactive polio vaccine is prepared by [[formaldehyde|formalin]] inactivation of three wild, virulent reference strains: Mahoney or Brunenders (PV-1), MEF-1/Lansing (PV-2), and Saukett/Leon (PV-3). Oral polio vaccine contains [[attenuated vaccine|live attenuated]] (weakened) strains of the three serotypes of poliovirus. [[Passaging]] the virus strains in monkey kidney epithelial cells introduces mutations in the viral IRES, and hinders (or attenuates) the ability of the virus to infect nerve tissue.<ref name=Kew_2005/>

Polioviruses were formerly classified as a distinct species belonging to the genus ''Enterovirus'' in the family ''Picornaviridae''. In 2008, ''Poliovirus'' ceased to be recognized as a species, and the three serotypes were assigned to the species ''Human enterovirus C'' (later renamed ''Enterovirus C'') in the genus ''Enterovirus'' in the family ''Picornaviridae''. The type species of the genus ''Enterovirus'' was changed from ''Poliovirus'' to {{nowrap|(Human) ''Enterovirus C''}}.<ref>{{cite journal | vauthors = Carstens EB, Ball LA | title = Ratification vote on taxonomic proposals to the International Committee on Taxonomy of Viruses (2008) | journal = Archives of Virology | volume = 154 | issue = 7 | pages = 1181–1188 | date = July 2009 | pmid = 19495937 | pmc = 7086627 | doi = 10.1007/s00705-009-0400-2 }}</ref>

== Pathogenesis ==
{{Main|Polio}}
[[Image:Polio EM PHIL 1875 lores.PNG|thumb|upright=0.8|[[Electron micrograph]] of poliovirus]]

The primary determinant of infection for any virus is its ability to enter a cell and produce additional infectious particles. The presence of CD155 is thought to define the animals and tissues that can be infected by poliovirus. CD155 is found (outside of laboratories) only on the cells of humans, higher [[primates]], and [[Old World monkey]]s. Poliovirus is, however, strictly a human pathogen, and does not naturally infect any other species (although [[Common chimpanzee|chimpanzee]]s and Old World monkeys can be experimentally infected).<ref>{{cite journal | vauthors = Mueller S, Wimmer E | title = Recruitment of nectin-3 to cell-cell junctions through trans-heterophilic interaction with CD155, a vitronectin and poliovirus receptor that localizes to alpha(v)beta3 integrin-containing membrane microdomains | journal = The Journal of Biological Chemistry | volume = 278 | issue = 33 | pages = 31251–31260 | date = August 2003 | pmid = 12759359 | doi = 10.1074/jbc.M304166200 | doi-access = free }}</ref>

The ''CD155'' gene appears to have been subject to [[positive selection]].<ref name="Suzuki2006">{{cite journal | vauthors = Suzuki Y | title = Ancient positive selection on CD155 as a possible cause for susceptibility to poliovirus infection in simians | journal = Gene | volume = 373 | pages = 16–22 | date = May 2006 | pmid = 16500041 | doi = 10.1016/j.gene.2005.12.016 }}</ref> The protein has several domains of which domain D1 contains the polio virus binding site. Within this domain, 37 amino acids are responsible for binding the virus.

Poliovirus is an [[enterovirus]]. Infection occurs via the [[fecal–oral route]], meaning that one ingests the virus and viral replication occurs in the [[gastrointestinal tract]].<ref name=Bodian_1965>{{cite book |vauthors=Bodian D, Horstmann DH|title=Polioviruse |publisher=Lippincott |location=Philadelphia, Penn |year=1969 |pages=430–73}}</ref> Virus is shed in the feces of infected individuals. In 95% of cases only a primary, transient presence of [[viremia]] (virus in the bloodstream) occurs, and the poliovirus infection is [[asymptomatic]]. In about 5% of cases, the virus spreads and replicates in other sites such as [[brown fat]], [[reticuloendothelial]] tissue, and [[muscle]]. The sustained viral replication causes secondary viremia and leads to the development of minor symptoms such as fever, headache, and sore throat.<ref>{{cite journal | vauthors = Sabin AB | title = Pathogenesis of poliomyelitis; reappraisal in the light of new data | journal = Science | volume = 123 | issue = 3209 | pages = 1151–1157 | date = June 1956 | pmid = 13337331 | doi = 10.1126/science.123.3209.1151 | bibcode = 1956Sci...123.1151S }}</ref> Paralytic poliomyelitis occurs in less than 1% of poliovirus infections. Paralytic 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 temporary or permanent [[paralysis]]. This is a very rare event in babies, who still have anti-poliovirus [[Antibody|antibodies]] acquired from their mothers.<ref>{{cite book | vauthors = Carter J, Saunders VA | chapter = Picornavirus |title=Virology: Principles and Applications |date=2007 |publisher=John Wiley & Sons |isbn=978-0-470-02386-0 |edition=1st |location=Chichester, England |oclc=124160564|page= 158 }}</ref> In rare cases, paralytic poliomyelitis leads to [[respiratory arrest]] and death. In cases of paralytic disease, muscle pain and spasms are frequently observed prior to onset of weakness and paralysis. Paralysis typically persists  from days to weeks prior to recovery.<ref>{{EMedicine|article|306440|Acute Poliomyelitis}}<br />{{EMedicine|article|967950|Pediatric Poliomyelitis}}</ref>

In many respects, the [[neurological]] phase of infection is thought to be an accidental diversion of the normal [[gastrointestinal]] infection.<ref name=Mueller/> The mechanisms by which poliovirus enters the CNS are poorly understood. Three nonmutually exclusive hypotheses have been suggested to explain its entry. All theories require primary viremia. The first hypothesis predicts that virions pass directly from the blood into the central nervous system by crossing the [[blood–brain barrier]] independent of CD155.<ref>{{cite journal | vauthors = Yang WX, Terasaki T, Shiroki K, Ohka S, Aoki J, Tanabe S, Nomura T, Terada E, Sugiyama Y, Nomoto A | title = Efficient delivery of circulating poliovirus to the central nervous system independently of poliovirus receptor | journal = Virology | volume = 229 | issue = 2 | pages = 421–428 | date = March 1997 | pmid = 9126254 | doi = 10.1006/viro.1997.8450 | doi-access = free }}</ref> A second hypothesis suggests that the virions are transported from peripheral tissues that have been bathed in the viremic blood, for example muscle tissue, to the spinal cord through nerve pathways via [[Retrograde transport|retrograde axonal transport]].<ref>{{cite journal | vauthors = Ohka S, Yang WX, Terada E, Iwasaki K, Nomoto A | title = Retrograde transport of intact poliovirus through the axon via the fast transport system | journal = Virology | volume = 250 | issue = 1 | pages = 67–75 | date = October 1998 | pmid = 9770421 | doi = 10.1006/viro.1998.9360 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Ren R, Racaniello VR | title = Poliovirus spreads from muscle to the central nervous system by neural pathways | journal = The Journal of Infectious Diseases | volume = 166 | issue = 4 | pages = 747–752 | date = October 1992 | pmid = 1326581 | doi = 10.1093/infdis/166.4.747 }}</ref><ref>{{cite journal | vauthors = Lancaster KZ, Pfeiffer JK | title = Limited trafficking of a neurotropic virus through inefficient retrograde axonal transport and the type I interferon response | journal = PLOS Pathogens | volume = 6 | issue = 3 | pages = e1000791 | date = March 2010 | pmid = 20221252 | pmc = 2832671 | doi = 10.1371/journal.ppat.1000791 | veditors = Gale Jr M | doi-access = free }}</ref> A third hypothesis is that the virus is imported into the CNS via infected [[monocyte]]s or [[macrophage]]s.<ref name=DeJesus/>

Poliomyelitis is a disease of the central nervous system. However, CD155 is believed to be present on the surface of most or all human cells. Therefore, receptor expression does not explain why poliovirus preferentially infects certain tissues. This suggests that tissue [[tropism]] is determined after cellular infection. Recent work has suggested that the [[interferon type I|type I interferon]] response (specifically that of interferon alpha and beta) is an important factor that defines which types of cells support poliovirus replication.<ref>{{cite journal | vauthors = Ida-Hosonuma M, Iwasaki T, Yoshikawa T, Nagata N, Sato Y, Sata T, Yoneyama M, Fujita T, Taya C, Yonekawa H, Koike S | title = The alpha/beta interferon response controls tissue tropism and pathogenicity of poliovirus | journal = Journal of Virology | volume = 79 | issue = 7 | pages = 4460–4469 | date = April 2005 | pmid = 15767446 | pmc = 1061561 | doi = 10.1128/JVI.79.7.4460-4469.2005 }}</ref> In mice expressing CD155 (through genetic engineering) but lacking the type I interferon receptor, poliovirus not only replicates in an expanded repertoire of tissue types, but these mice are also able to be infected orally with the virus.<ref>{{cite journal | vauthors = Ohka S, Igarashi H, Nagata N, Sakai M, Koike S, Nochi T, Kiyono H, Nomoto A | title = Establishment of a poliovirus oral infection system in human poliovirus receptor-expressing transgenic mice that are deficient in alpha/beta interferon receptor | journal = Journal of Virology | volume = 81 | issue = 15 | pages = 7902–7912 | date = August 2007 | pmid = 17507470 | pmc = 1951287 | doi = 10.1128/JVI.02675-06 }}</ref>

== Immune system avoidance ==
[[File:CD155 molecules complexed with a poliovirus particle.png|thumb|upright=0.8|CD155 molecules complexed with a poliovirus particle.
Reconstructed image from cryo-electron microscopy.]]

Poliovirus has two key mechanisms to evade the [[immune system]]. First, it can survive the highly [[acidic]] conditions of the stomach, allowing ingested viruses to infect the host and spread throughout the body via the [[lymphatic system]].<ref name="Goodsell" /> Second, because it can replicate very quickly, the virus overwhelms the host's organs before an immune response can be mounted.<ref name="Racaniello2006">{{cite journal | vauthors = Racaniello VR | title = One hundred years of poliovirus pathogenesis | journal = Virology | volume = 344 | issue = 1 | pages = 9–16 | date = January 2006 | pmid = 16364730 | doi = 10.1016/j.virol.2005.09.015 | doi-access = free }}</ref> If detail is given at the attachment phase; poliovirus with canyons on the virion surface have virus attachment sites located in pockets at the canyon bases. The canyons are too narrow for access by [[Antibody|antibodies]], so the virus attachment sites are protected from the host's immune surveillance, while the remainder of the virion surface can mutate to avoid the host's immune response.<ref>{{cite book | chapter = Picornavirus replication |title=Virology: Principles and Applications | vauthors = Carter J, Saunders VA |publisher=John Wiley & Sons|year=2007|isbn=978-0-470-02386-0|location=Liverpool John Moores University, UK|page=162}}</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.<ref>{{Cite web |url=https://www.who.int/biologicals/areas/vaccines/poliomyelitis/en/ |archive-url=https://web.archive.org/web/20140517023039/http://www.who.int/biologicals/areas/vaccines/poliomyelitis/en/ |url-status=dead |archive-date=May 17, 2014 |title=WHO &#124; Poliomyelitis}}</ref>

== Eradication ==
{{Excerpt|Polio eradication}}

== Research ==

=== Transgenic mice ===
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 | vauthors = 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 = 353–362 | date = October 1990 | pmid = 2170026 | doi = 10.1016/0092-8674(90)90168-E | s2cid = 11946113 | doi-access = free }}</ref><ref name="pmid1846972">{{cite journal | vauthors = Koike S, Taya C, Kurata T, Abe S, Ise I, Yonekawa H, Nomoto A | title = Transgenic mice susceptible to poliovirus | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 88 | issue = 3 | pages = 951–955 | date = February 1991 | pmid = 1846972 | pmc = 50932 | doi = 10.1073/pnas.88.3.951 | doi-access = free | bibcode = 1991PNAS...88..951K }}</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 | vauthors = Horie H, Koike S, Kurata T, Sato-Yoshida Y, Ise I, Ota Y, Abe S, Hioki K, Kato H, Taya C | title = Transgenic mice carrying the human poliovirus receptor: new animal models for study of poliovirus neurovirulence | journal = Journal of Virology | volume = 68 | issue = 2 | pages = 681–688 | date = February 1994 | pmid = 8289371 | pmc = 236503 | doi = 10.1128/JVI.68.2.681-688.1994 }}</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 | vauthors = Ohka S, Nomoto A | title = Recent insights into poliovirus pathogenesis | journal = Trends in Microbiology | volume = 9 | issue = 10 | pages = 501–506 | date = October 2001 | pmid = 11597452 | doi = 10.1016/S0966-842X(01)02200-4 }}</ref>

Three distinct types of TgPVR mice have been well studied:<ref name="pmid7832641">{{cite journal | vauthors = Koike S, Taya C, Aoki J, Matsuda Y, Ise I, Takeda H, Matsuzaki T, Amanuma H, Yonekawa H, Nomoto A | title = Characterization of three different transgenic mouse lines that carry human poliovirus receptor gene--influence of the transgene expression on pathogenesis | journal = Archives of Virology | volume = 139 | issue = 3–4 | pages = 351–363 | year = 1994 | pmid = 7832641 | doi = 10.1007/BF01310797 | s2cid = 11070024 }}</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 | vauthors = Nagata N, Iwasaki T, Ami Y, Sato Y, Hatano I, Harashima A, Suzaki Y, Yoshii T, Hashikawa T, Sata T, Horiuchi Y, Koike S, Kurata T, Nomoto A | title = A poliomyelitis model through mucosal infection in transgenic mice bearing human poliovirus receptor, TgPVR21 | journal = Virology | volume = 321 | issue = 1 | pages = 87–100 | date = March 2004 | pmid = 15033568 | doi = 10.1016/j.virol.2003.12.008 | doi-access =  }}</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.
*A fourth TgPVR mouse model - these "cPVR" mice carry hPVR [[cDNA]], driven by a β-[[actin]] [[promoter (biology)|promoter]], and have proven susceptible to poliovirus through intracerebral, intramuscular, and intranasal routes. In addition, these mice are capable of developing the [[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 | vauthors = Dragunsky E, Nomura T, Karpinski K, Furesz J, Wood DJ, Pervikov Y, Abe S, Kurata T, Vanloocke O, Karganova G, Taffs R, Heath A, Ivshina A, Levenbook I | title = Transgenic mice as an alternative to monkeys for neurovirulence testing of live oral poliovirus vaccine: validation by a WHO collaborative study | journal = Bulletin of the World Health Organization | volume = 81 | issue = 4 | pages = 251–260 | year = 2003 | pmid = 12764491 | pmc = 2572431 | url = https://www.scielosp.org/article/bwho/2003.v81n4/251-260/en/ | access-date = 2022-04-01 | url-status = live | archive-url = https://web.archive.org/web/20210224202212/https://scielosp.org/article/bwho/2003.v81n4/251-260/en/ | archive-date = 2021-02-24 }}</ref>

=== Genetic modification ===
A modification of the poliovirus, called [[PVSRIPO]], was tested in early clinical trials as a possible treatment for cancer.<ref name="brown14">{{cite journal | vauthors = Brown MC, Dobrikova EY, Dobrikov MI, Walton RW, Gemberling SL, Nair SK, Desjardins A, Sampson JH, Friedman HS, Friedman AH, Tyler DS, Bigner DD, Gromeier M | title = Oncolytic polio virotherapy of cancer | journal = Cancer | volume = 120 | issue = 21 | pages = 3277–3286 | date = November 2014 | pmid = 24939611 | pmc = 4205207 | doi = 10.1002/cncr.28862 }}</ref> {{As of|2022|September}}, a number of clinical trials are under way.<ref>{{Cite web |date=2022-09-01 |title=Update on Recombinant Poliovirus Cancer Immunotherapy |url=https://tischbraintumorcenter.duke.edu/stories/update-recombinant-poliovirus-cancer-immunotherapy |access-date=2024-08-10 |website=Tisch Brain Tumor Center |language=en}}</ref><ref>{{Cite web |last=UCSF |date=2017-06-01 |title=UCSF Glioma Trial: PVSRIPO in Recurrent Malignant Glioma |url=https://clinicaltrials.ucsf.edu/trial/NCT02986178 |access-date=2024-08-10 |website=clinicaltrials.ucsf.edu |language=en}}</ref>

A drawback of the attenuated virus used in the Sabin oral polio vaccine is its potential to cause vaccine-associated paralytic poliomyelitis (VAPP) in approximately one individual per every 2.7{{nbsp}}million doses administered.<ref name="GPEI-OPV">{{cite web |title=OPV - Oral Polio Vaccine |url=https://polioeradication.org/polio-today/polio-prevention/the-vaccines/opv/ |archive-url= |archive-date= |access-date=9 August 2024 |website=Global Polio Eradication Initiative (GPEI) |publisher=}}</ref> In addition, the live virus can also circulate in under-vaccinated populations (circulating vaccine-derived poliovirus, cVDPV) and over time can revert to a neurovirulent form causing paralytic polio.<ref name="GPEI-OPV" /> Researchers have developed a poliovirus type 2 vaccine strain that is genetically more stable and less likely to regain virulence than the original Sabin2 strain, with three key genetic modifications.<ref>{{cite journal | vauthors = Yeh MT, Bujaki E, Dolan PT, Smith M, Wahid R, Konz J, Weiner AJ, Bandyopadhyay AS, Van Damme P, De Coster I, Revets H, Macadam A, Andino R | title = Engineering the Live-Attenuated Polio Vaccine to Prevent Reversion to Virulence | journal = Cell Host & Microbe | volume = 27 | issue = 5 | pages = 736–751.e8 | date = May 2020 | pmid = 32330425 | pmc = 7566161 | doi = 10.1016/j.chom.2020.04.003 }}</ref> The vaccine derived from this strain, novel oral polio virus type 2 (nOPV2), was granted emergency licencing in 2021, and subsequently full licensure in December 2023.<ref name=":x2">{{Cite web |date=12 April 2024 |title=GPEI-OPV Oral polio vaccine |url=https://polioeradication.org/polio-today/polio-prevention/the-vaccines/opv/ |access-date=12 April 2024 |website=Global Polio Eradication Initiative - World Health Organization |language=en-GB}}</ref> Genetically stabilsed vaccines targeting poliovirus types 1 and 3 are in development, with the intention that these will eventually completely replace the Sabin vaccines.<ref>{{Cite web | vauthors = Gadye L |date=2023-06-14 |title=Two New Vaccines Join the Fight to Eradicate Polio |url=https://www.ucsf.edu/news/2023/06/425601/two-new-vaccines-join-fight-eradicate-polio |access-date=2024-08-10 |website=The University of California San Francisco |language=en}}</ref>

== History ==

=== Discovery ===
Poliovirus was first isolated in 1909 by [[Karl Landsteiner]] and [[Erwin Popper]].<ref name="Paul_1971">{{cite book | vauthors = Paul JR |title=A History of Poliomyelitis |publisher=Yale University Press |location=New Haven, Conn |year=1971 |isbn=978-0-300-01324-5 | series = (Yale studies in the history of science and medicine)|page=}}{{page needed|date=August 2021}}</ref> The structure of the virus was first elucidated in 1958 using [[X-ray diffraction]] by a team at [[Birkbeck College]] led by [[Rosalind Franklin]],<ref>{{cite web |title=Behind the picture: Rosalind Franklin and the polio model |url=http://www.insight.mrc.ac.uk/2013/07/24/behind-the-picture-rosalind-franklin-and-the-polio-model/#more-2575 |publisher=Medical Research Council |access-date=4 September 2019 |date=2019-03-14 |archive-date=2018-10-30 |archive-url=https://web.archive.org/web/20181030132842/https://www.insight.mrc.ac.uk/2013/07/24/behind-the-picture-rosalind-franklin-and-the-polio-model/#more-2575 |url-status=dead }}</ref><ref>{{cite book | vauthors = Maddox B |title=Rosalind Franklin: The Dark Lady of DNA |year=2003 |page=296 |publisher=Harper Collins |location=London |isbn=0-00-655211-0 |url=https://books.google.com/books?id=YbTh44KfkPIC |access-date=2020-05-15 |archive-date=2023-01-14 |archive-url=https://web.archive.org/web/20230114012049/https://books.google.com/books?id=YbTh44KfkPIC |url-status=live }}</ref> showing the polio virus to have icosahedral symmetry.<ref>{{cite book | vauthors = Brown A |title=J.D. Bernal: The Sage of Science |year=2007 |publisher=Oxford University Press |pages= 359–61 |location=New York |isbn=978-0-19-920565-3}}</ref>

=== Genome ===
In 1981, the poliovirus genome was published by two different teams of researchers: by [[Vincent Racaniello]] and [[David Baltimore]] at [[Massachusetts Institute of Technology|MIT]]<ref name="Racaniello1981">{{cite journal | vauthors = Racaniello VR, Baltimore D | title = Molecular cloning of poliovirus cDNA and determination of the complete nucleotide sequence of the viral genome | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 78 | issue = 8 | pages = 4887–4891 | date = August 1981 | pmid = 6272282 | pmc = 320284 | doi = 10.1073/pnas.78.8.4887 | doi-access = free | bibcode = 1981PNAS...78.4887R }}</ref> and by [[Naomi Kitamura]] and [[Eckard Wimmer]] at [[Stony Brook University]].<ref name="Kitamura">{{cite journal | vauthors = Kitamura N, Semler BL, Rothberg PG, Larsen GR, Adler CJ, Dorner AJ, Emini EA, Hanecak R, Lee JJ, van der Werf S, Anderson CW, Wimmer E | title = Primary structure, gene organization and polypeptide expression of poliovirus RNA | journal = Nature | volume = 291 | issue = 5816 | pages = 547–553 | date = June 1981 | pmid = 6264310 | doi = 10.1038/291547a0 | s2cid = 4352308 | bibcode = 1981Natur.291..547K }}</ref>

=== Structure ===
The three-dimensional structure of poliovirus was determined in 1985 by [[James Hogle]] at [[Scripps Research Institute]] using X-ray crystallography.<ref name="Hogle1985">{{cite journal | vauthors = Hogle JM, Chow M, Filman DJ | title = Three-dimensional structure of poliovirus at 2.9 A resolution | journal = Science | volume = 229 | issue = 4720 | pages = 1358–1365 | date = September 1985 | pmid = 2994218 | doi = 10.1126/science.2994218 }}</ref>

=== Cloning and synthesis ===
[[File:Poliovirus binding receptor 1DGI.png|thumb|upright=0.8|Model of poliovirus-binding CD155 (shown in purple)]]
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 | vauthors = Racaniello VR, Baltimore D | title = Cloned poliovirus complementary DNA is infectious in mammalian cells | journal = Science | volume = 214 | issue = 4523 | pages = 916–919 | date = November 1981 | pmid = 6272391 | doi = 10.1126/science.6272391 | bibcode = 1981Sci...214..916R }}</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, [[Eckard Wimmer]]'s group at [[Stony Brook University]] succeeded in synthesizing poliovirus from its chemical code, producing the world's first synthetic virus.<ref>{{cite journal | vauthors = 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 = 1016–1018 | date = August 2002 | pmid = 12114528 | doi = 10.1126/science.1072266 | s2cid = 5810309 | doi-access = free | bibcode = 2002Sci...297.1016C }}</ref> Scientists first converted poliovirus's published RNA sequence, 7741 bases long, into a DNA sequence, as DNA was easier to synthesize. Short fragments of this DNA sequence were obtained by mail-order, and assembled. The complete viral genome 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. Other enzymes were then used to translate the RNA into a polypeptide, producing functional viral particle. This whole painstaking process took two years. 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 weaker than the original virus, probably due to one of the added markers.<ref>{{cite journal | vauthors = Couzin J | title = Virology. Active poliovirus baked from scratch | journal = Science | volume = 297 | issue = 5579 | pages = 174–175 | date = July 2002 | pmid = 12114601 | doi = 10.1126/science.297.5579.174b | s2cid = 83531627 }}</ref>

== References ==
{{Reflist|30em}}

== External links ==
{{Portal|Medicine|Viruses}}

*[https://www.ncbi.nlm.nih.gov/ICTVdb/ICTVdB/00.052.0.01.001.htm ICTVdb virus classification 2006]
*[http://www.picornaviridae.com/enterovirus/enterovirus.htm Home of Picornaviruses (latest updates of species, serotypes, & proposed changes)] {{Webarchive|url=https://web.archive.org/web/20101104143822/http://www.picornaviridae.com/enterovirus/enterovirus.htm |date=2010-11-04 }}
* {{cite web | vauthors = Goodsell D |title=Poliovirus and Rhinovirus |work=August 2001 Molecule of the Month |url=http://www.pdb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/pdb20_1.html |access-date=2010-01-07 |archive-date=2011-03-03 |archive-url=https://web.archive.org/web/20110303221109/http://www.pdb.org/pdb/static.do?p=education_discussion%2Fmolecule_of_the_month%2Fpdb20_1.html |url-status=dead }}
*[http://www.pdbe.org/emsearch/polio* 3D macromolecular structures of the Poliovirus archived in the EM Data Bank(EMDB)]
* {{cite web |title=Human poliovirus 1 |work=NCBI Taxonomy Browser |url=https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=12080 |id=12080}}
* {{cite web |title=Human poliovirus 3 |work=NCBI Taxonomy Browser |url=https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=12086 |id=12086}}

{{Viral diseases}}
{{Viral proteins}}
{{Taxonbar|from=Q12438936}}
{{Authority control}}

<!--     CATEGORIES     -->
[[Category:Human viruses]]
[[Category:Viruses described in 1909]]
[[Category:Human viruses described in 1909]]
[[Category:Enteroviruses]]
[[Category:Polio]]
[[Category:Infraspecific virus taxa]]