Poliovirus

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Poliovirus
Polio.jpg

Poliovirus (negatively stained TEM image; bar: 50 nm)

Systematics
Classification : Viruses
Area : Riboviria
Empire : Orthornavirae
Phylum : Pisuviricota
Class : Pisoniviricetes
Order : Picornavirales
Family : Picornaviridae
Genre : Enterovirus
Type : Enterovirus C
Subspecies : Human poliovirus
Taxonomic characteristics
Genome : (+) ssRNA linear
Baltimore : Group 4
Symmetry : icosahedral
Cover : no
Scientific name
Enterovirus C
Left

The poliovirus (more precisely human poliovirus , occasionally poliomyelitis virus , PV ) is a subspecies of viruses of the species Enterovirus C ( EV-C ) from the genus Enterovirus in the family Picornaviridae . The poliovirus triggers polio ( poliomyelitis , polio for short) in humans . It is a very simple virus without an envelope with a genome of single-stranded plus RNA . It is found in humans and some other primates. Eradicating poliovirus through vaccination is a goal of the World Health Organization . In Germany it is already considered to be eradicated.

Discovery and History

Although poliomyelitis was a long-known disease, it was only after studies by Swedish doctor Ivar Wickman at the beginning of the 20th century that it became generally accepted that it was a contact-borne infectious disease . Karl Landsteiner and Erwin Popper are considered to be the discoverers of the polio virus ; In 1908 they succeeded in transmitting the pathogen to two monkeys by injecting a bacteriologically sterile spinal cord extract from a boy who had died of poliomyelitis; both animals fell ill.

Charles Armstrong managed to transmit the virus to cotton rats in the 1930s . John F. Enders , Frederick Chapman Robbins and Thomas Huckle Weller were able to multiply the virus in cell cultures in 1949; for this they were jointly awarded the Nobel Prize for Physiology or Medicine in 1954 . In 1955, an inactivated polio vaccine developed by Jonas Salk was approved, and in 1960 an oral vaccine by Albert Sabin .

2010 broke a mutated virus variant ( English circulating vaccine-derived poliovirus , cVDPV) vaccine protection in the Republic of Congo and caused a serious outbreak, several hundred people have been infected in the course and passed away almost half of them.

Virus build-up

morphology

The approximately round, unenveloped virus particle has a diameter of 28 to 30 nanometers . In 1985 it was possible to resolve the three-dimensional structure of a complete poliovirus particle by means of crystal structure analysis. Each virion contains a copy of the single-stranded RNA genome, which is encased in an icosahedral capsid . The capsid is made up of 60 copies of each of the four capsid proteins VP1, VP2, VP3 and VP4.

Because of this structure, the poliovirus is a relatively environmentally stable virus that, as an unenveloped virus, is only slowly inactivated by disinfectants such as 70 percent ethanol or isopropanol . It is therefore one of those viruses on which disinfectants have to prove their effectiveness in the approval process. The virus is also only slowly inactivated by many detergents , by quaternary ammonium compounds or by acids such as gastric acid .

Genome and Virus Proteins

The genomic structure of the type 1 poliovirus

The viral genome was first cloned and sequenced in 1981 . The RNA of type 1 7440 nucleotides long , at the 5 'end of which a viral protein (VPg) is bound, consists of a long 5' untranslated region (5 'NTR), which is followed by a single open reading frame , which encodes a polyprotein of 220  kDa , as well as a short 3'-untranslated region (3'-NTR) with a poly (A) tail . In the 5 'untranslated area, the RNA contains an internal ribosomal entry point (IRES) , which is crucial for the translation of the RNA in the host cell. Mutations in the IRES are a molecular cause of the attenuation of the polioviruses used in oral polio vaccines .

The 220 kDa polyprotein is broken down into three proteins, P1, P2 and P3 , by viral peptidases ; the P1 protein is broken down further into the structural proteins VP1-VP4, from which the capsid of the new virus particles is assembled. The proteins P2 and P3 give rise to non-structural proteins that have a role in the replication of the virus. Proteins 2A pro and 3C pro as well as 3CD pro are peptidases that break down the viral polyprotein, while proteins 2BC, 2C and 3AB form a membrane complex that is required for virus replication. 3B VPg binds to the 5 'end of the viral RNA and is important for the initiation of the replication of the RNA. Finally , 3D pol is an RNA-dependent RNA polymerase that synthesizes the viral RNA.

Replication

The poliovirus multiplies in the host cell's cytoplasm . In order to be able to enter the cell, the virus needs a specific receptor , the CD155 protein . The virus can then transfer its RNA into the cell, where it is immediately translated into the polyprotein . The polyprotein can proteolytically break down into individual structural and functional proteins. The RNA is not only translated but also replicated . The latter happens through the viral RNA-dependent RNA polymerase 3D pol , which converts the original plus-RNA into a minus-RNA and from this immediately generates new plus-RNA. The RNA is finally packaged with the structural proteins to form a new virus particle (virion); eventually the host cell dies and the viruses are released.

Systematics

The poliovirus belongs to the enterovirus genus ; this is part of the Picornaviridae family . Three serotypes are distinguished in the poliovirus .

  • Order picornavirales
  • Family Picornaviridae
  • Enterovirus genus
  • Species Enterovirus C (EV-C)
  • Subspecies Human Enterovirus C (HEV-C)
  • Subspecies (Human) Poliovirus (PV, HPV)
  • Serotype 1 (PV1, type "Mahoney" or "Brunhilde"): this type is the most common and can also cause serious illness.
  • Serotype 2 (PV2, type “Lansing”): this type causes rather mild progression (has been considered eradicated since 2015).
  • Serotype 3 (PV3, type "Saukett" or "Leon"): this type occurs rather rarely, but usually causes a serious course (has been eradicated since 2019).

The three serotypes differ structurally mainly in the capsid proteins. Comparisons of the complete genome sequences of the polioviruses and the human enterovirus C (HEV-C) showed that the polioviruses and the HEV-C viruses are very similar in genome structure to one another. Outside the capsid region, the polioviruses are similar to the HEV-C viruses as they are to each other. It was therefore proposed to abandon the poliovirus species and classify the three serotypes in the enterovirus C species (today's name, as of November 2018).

Diffusion, transmission and specificity

Spread and eradication

Originally the virus was spread around the world; in the tropics, epidemics occurred year-round, in temperate latitudes especially in summer. In endemic areas, the virus can also be detected in sewage, among other things; in the environment it should remain capable of reproduction for several weeks. The only natural host and thus the only known reservoir is humans. Hence, vaccination seems possible. In fact, the wild poliovirus type 2 (WPV2) has not been detected since 1999. In 2007 there were 1,310 cases of wild virus poliomyelitis worldwide. In 2008, the virus was only endemic to Nigeria, India, Pakistan and Afghanistan . Polio wild virus 3 (WPV3) was last detected in Nigeria in 2012. In 2015, type 2 was declared eradicated by the WHO. On World Polio Day 2019, the WHO also declared type 3 to be eradicated.

Transmission and specificity

The virus is transmitted by smear infection and also through objects. The tropism of the poliovirus is limited to humans and some other primates. Various monkeys can be infected experimentally by injecting the virus directly into the spinal cord or brain . Only chimpanzees and old world monkeys can also be infected orally like humans . Since the virus requires a specific receptor , the CD155 protein, on the host cells for infection, the infection of an organism essentially depends on whether the virus can bind to the receptor in the host. The poliovirus binds to CD155 from humans, chimpanzees and Old World monkeys, but only partially to CD155 from New World monkeys . After binding to the CD155 receptor, the virus is taken up into the cell, where it can multiply. The multiplication mechanisms within the cell are less host-specific than the uptake mechanism. The CD155 receptor is located on the cell surface of monocytes , macrophages , T lymphocytes and nerve cells. Lymphatic tissues such as Peyer's plaques in the intestine are the site of the first virus replication.

Disease, Detection, and Vaccines

illness

After the virus has been ingested by mouth and multiplied in the nasopharynx and digestive tract , viraemia occurs , in which the virus is spread through the bloodstream. In most cases this is symptomatic; flu-like symptoms only occur in 4 to 8% of those infected.

Only in rare cases, in around 1% of infections, do the viruses also attack nerve cells , preferably the anterior horn cells in the spinal cord, which are important for the muscles . This then leads to the clinical picture of polio.

proof

The virus can be detected from stool samples, throat swabs and, if necessary, from CSF . With classic virological detection, the prepared material is incubated on cell cultures and the identity of the virus is determined using a neutralization test with specific antisera. Isolation of the virus from stool samples should be 80% successful in the first 14 days of the disease. This method is complex, however. This is why the reverse transcriptase-polymerase chain reaction is often used today, with which viral RNA can be detected directly in clinical material. Sometimes even parts of the virus genome are sequenced in order to establish connections between different patients via sequence comparisons and to be able to understand the path of infection. A detection of antibodies against the virus in the patient's serum can also be carried out.

Reporting requirement

In Germany, direct or indirect evidence of the poliovirus must be reported by name in accordance with Section 7 of the Infection Protection Act (IfSG) if the evidence indicates an acute infection. This reporting obligation for the pathogen primarily affects laboratories and their lines (cf. § 8 IfSG).

In Switzerland, the positive laboratory analytical finding is a poliovirus laboratory reportable namely after the Epidemics Act (EpG) in connection with the epidemic Regulation and Annex 3 of the Regulation of EDI on the reporting of observations of communicable diseases of man .

Vaccines

There are two different polio vaccines:

  • The inactivated poliovaccine (IPV) according to Jonas E. Salk (also: Salk vaccine) is a dead vaccine that is injected intramuscularly . The vaccine contains formaldehyde- inactivated virus particles of the three types ("trivalent") grown on cell cultures . This vaccine offers good protection against the disease; the decisive advantage of this vaccine is that vaccination poliomyelitis is excluded. The inactivated polio vaccine was approved in the USA in 1955 and led to a rapid decline in the number of diseases there. As a combination vaccine, IPV can also be used with other vaccines, e.g. B. against tetanus and diphtheria available (Td-IPV vaccine).
  • The oral polio vaccine (OPV) by Albert Sabin (also: Sabin vaccine) for the oral vaccine is an inserted live vaccine and consists of a mixture of the three types of so-called attenuated viruses that are still capable of reproduction, but no more sickness excite (lack of neurotoxicity) . The vaccine creates an inapparent infection in the gastrointestinal tract . The advantage of this vaccine, in addition to its simple application, is that it also creates immunity in the gastrointestinal tract ( IgA mucosal immunity), which not only prevents the disease but also the transmission of the virus. In immunodeficiencies and immunosuppression OPV is contraindicated .

The live vaccine is no longer used in Germany because vaccination poliomyelitis, especially in patients with immunodeficiencies (especially agammaglobulinaemia ), cannot be completely ruled out. Since the poliovirus has been eradicated in Germany, this would be an unacceptable risk. The WHO, on the other hand, uses the live vaccine as part of the global poliomyelitis eradication program.

Individual evidence

  1. ICTV Master Species List 2018b.v2 MSL # 34v, March 2019
  2. a b c d ICTV: ICTV Taxonomy history: Enterovirus C , EC 51, Berlin, Germany, July 2019; Email ratification March 2020 (MSL # 35)
  3. International Committee on Taxonomy of Viruses (ICTV): Master Species List 2018a v1 , MSL including all taxa updates since the 2017 release. Fall 2018 (MSL # 33)
  4. ViralZone: ICTV 2016 Master Species List # 31 with Acronyms, (Excel XLSX) , SIB Swiss Institute of Bioinformatics
  5. Hans J. Eggers: Milestones in early poliomyelitis research (1840 to 1949) . In: Journal of Virology . tape 73 , no. 6 , June 1999, p. 4533-4535 , PMID 10233910 .
  6. Jan Felix Drexler et al .: Robustness against serum neutralization of a poliovirus type 1 from a lethal epidemic of poliomyelitis in the Republic of Congo in 2010 . In: Proceedings of the National Academy of Sciences of the United States of America . tape 111 , no. 35 , September 2, 2014, p. 12889-12894 , doi : 10.1073 / pnas.1323502111 , PMID 25136105 , PMC 4156724 (free full text).
  7. ^ JM Hogle et al .: Three-dimensional structure of poliovirus at 2.9 A resolution . In: Science (New York, NY) . tape 229 , no. 4720 , September 27, 1985, pp. 1358-1365 , doi : 10.1126 / science.2994218 , PMID 2994218 .
  8. Testing and declaration of the effectiveness of disinfectants against viruses. In: Federal Health Gazette - Health Research - Health Protection. 2004, Volume 47, pp. 62-66. doi: 10.1007 / s00103-003-0754-7 . (PDF) ( Memento of the original from October 21, 2013 in the Internet Archive ) Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. . Retrieved May 24, 2013. @1@ 2Template: Webachiv / IABot / www.rki.de
  9. J. Steinmann et al .: Comparison of virucidal activity of alcohol-based hand sanitizers versus antimicrobial hand soaps in vitro and in vivo . In: The Journal of Hospital Infection . tape 82 , no. 4 , December 2012, p. 277–280 , doi : 10.1016 / j.jhin.2012.08.005 , PMID 23009803 .
  10. a b Nidia H. De Jesus: Epidemics to eradication: the modern history of poliomyelitis . In: Virology Journal . tape 4 , July 10, 2007, p. 70 , doi : 10.1186 / 1743-422X-4-70 , PMID 17623069 , PMC 1947962 (free full text).
  11. Betty Brown et al .: Complete genomic sequencing shows that polioviruses and members of human enterovirus species C are closely related in the noncapsid coding region . In: Journal of Virology . tape 77 , no. 16 , August 2003, p. 8973-8984 , doi : 10.1128 / jvi.77.16.8973-8984.2003 , PMID 12885914 .
  12. ^ Centers for Disease Control and Prevention (CDC). Progress toward interruption of wild poliovirus transmission - worldwide, January 2007-April 2008. In: MMWR Morb Mortal Wkly Rep. 57 (18), May 9, 2008, pp. 489-494. PMID 18463607
  13. Distribution map 2006 ( memento from September 25, 2006 in the web archive archive.today ) for the polio virus (polioeradication.org)
  14. Two out of three wild poliovirus strains eradicated: Global eradication of wild poliovirus type 3 declared on World Polio Day , online October 24, 2019, accessed October 24, 2019
  15. Shaukat Khan et al .: Characterization of the New World monkey homologues of human poliovirus receptor CD155 . In: Journal of Virology . tape 82 , no. July 14 , 2008, p. 7167-7179 , doi : 10.1128 / JVI.02664-07 , PMID 18480448 , PMC 2446954 (free full text).
  16. Leaflet on Poliomyelitis. of the Robert Koch Institute In: Epidemiological Bulletin . 1/2010, pp. 5-8.
  17. a b c d e Albert Heim: Picornaviruses . In: Sebastian Suerbaum, Gerd-Dieter Burchard, Stefan HE Kaufmann, Thomas F. Schulz (eds.): Medical microbiology and infectious diseases . Springer-Verlag, 2016, ISBN 978-3-662-48678-8 , pp. 459 , doi : 10.1007 / 978-3-662-48678-8_55 .

literature

  • David M. Knipe, Peter M. Howley (Red.): Fields' Virology. 5th edition. 2 volumes. Philadelphia 2007, ISBN 978-0-7817-6060-7 , pp. 796-884.
  • Anonymous: Global polio eradication - between fear and confidence. In: Hygiene and Medicine. 29 (11), 2004, pp. 400-401. ISSN  0172-3790

Web links