Poliovirus

The polio virus is a virus of the family Picornaviridae that causes polio or poliomyelitis in humans. It is a very simple virus without envelope with a genome of single-stranded plus RNA. It occurs in humans and some other primates; the eradication of poliovirus vaccine is a goal of the World Health Organization.

• 4.1 dissemination
• 4.2 Transmission and specificity

• 5.1 disease
• 5.2 proof
• 5.3 vaccines

Discovery and history

Although poliomyelitis a long-known disease was, was at the beginning of the 20th century generally recognized only after studies of the Swedish physician Ivar Wickman, that it is a transmitted by contact infection. As the discoverer of the polio virus but are Karl Landsteiner and Erwin Popper; In 1908, they managed to transfer by injection of a bacteriologically sterile spinal cord extract from a late poliomyelitis boys the pathogen on two monkeys; both diseased animals.

Charles Armstrong succeeded in the 1930s, to transmit the virus to cotton rats. John F. Enders, Frederick Chapman Robbins and Thomas Huckle Weller 1949 could multiply the virus in cell cultures; for they received in 1954 shared the Nobel Prize in Physiology or Medicine. 1955, developed by Jonas Salk inactivated polio vaccine was approved a few years later followed by an oral polio vaccine by Albert Sabin.

Virus assembly

Morphology

The nearly round nonenveloped virus particle has a diameter of 28 to 30 nanometers. 1985 succeeded to resolve the three-dimensional structure of a complete polio virus particle by crystal structure analysis. Each virion includes a copy of the single-stranded RNA genome, which is enclosed by an icosahedral capsid. The capsid consists of 60 copies each of four capsid proteins VP1, VP2, VP3 and VP4 together.

Due to this structure, the polio virus is a relatively environmentally stable virus is inactivated as a non-enveloped virus slowly by disinfectants such as 70 -percent ethanol or isopropanol, and therefore is in the group of viruses that need to be tested for the authorization procedure for disinfectants. By many detergents, quaternary ammonium compounds, or by acids, for example, gastric acid, the virus is inactivated slowly.

Genome and viral proteins

The viral genome was first cloned and sequenced in 1981. The 7440 nucleotides long RNA is, at the 5 'end of a viral protein ( VPg ) bound in type 1, 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, and a short 3'- untranslated region (3'- NTR ) with a poly ( a) tail. In the 5'- untranslated region of the RNA containing an internal ribosomal entry site (IRES ), which is decisive for the translation of the RNA in the host cell. Mutations in the IRES are a molecular cause for the attenuation of polioviruses used for oral polio vaccines.

The 220 ​​kDa polyprotein is divided by viral peptidases in three proteins, P1, P2 and P3; the P1 protein is further divided into the structural proteins VP1 -VP4, of which the capsid of the new virus particles are assembled. Go from the proteins P2 and P3 out non-structural proteins, which have a function in the replication of the virus. Proteins and 2Apro 3Cpro and 3CDpro are peptidases which break up the viral polyprotein 2BC during the proteins, 2C and 3AB form a membrane complex which is required for virus replication. 3BVPg binds to the 5'-end of the viral RNA, and is important for the initiation of replication of the RNA 3Dpol finally is a RNA-dependent RNA polymerase, the synthesized viral RNA.

Replication

Poliovirus replicates in the cytoplasm of the host cell. In order to enter the cell, the virus needs a specific receptor, the CD155 protein. Then the virus can transmit its RNA into the cell, where it is translated directly to the polyprotein. The polyprotein is proteolytically themselves decompose into individual structural and functional proteins. The RNA is not only translated but also replicated. This is done by the viral RNA - dependent RNA polymerase 3Dpol circumscribing the original plus RNA in a negative RNA and this once again creates new plus RNA. The RNA is finally packaged with the structural proteins to form a new virion; finally dies, the host cell and the virus to be released.

System

The polio virus belongs to the genus Enterovirus virus; this is part of the family Picornaviridae. When poliovirus three serotypes are distinguished.

• Family Picornaviridae genus enterovirus Species poliovirus Serotype 1 (type " Mahoney " or " Brunhilde " ): This type is the most common and can also cause serious illness.
• Serotype 2 (type " Lansing " ): this type is causing rather light curves.
• Serotype 3 (type "Leon" ): this type occurs rarely, but usually causes a serious course.

The three serotypes are structurally different, especially in the capsid proteins. Comparisons of the complete genome sequences of polio viruses and the human enterovirus C ( HEV C) showed that the polio virus and the HEV -C viruses are very similar to each other in the genomic structure. Outside the capsid region, the polio virus to the HEV - C viruses are so similar to each other. Therefore, it was proposed to abandon the species poliovirus and classify the three serotypes in the species Human enterovirus C. It has not been decided yet.

Distribution, transmission and specificity

Dissemination

Originally, the virus had spread throughout the world; epidemics occurred in the tropics all year round in temperate latitudes, especially in the summer. In areas endemic for the virus among others in wastewaters is detectable; in the environment it is to remain for several weeks capable of reproduction. The only natural host, and thus the only known reservoir is man. Therefore, eradication by vaccination seems possible; the polio virus type 2 which is already managed. In 2007, there were 1310 cases of the disease worldwide by wild polioviruses, in 2008, the virus is endemic only in Nigeria, India, Pakistan and Afghanistan.

Transmission and specificity

The virus is transmitted by contact infection (faecal -oral) and also about objects. The tropism of poliovirus is restricted to humans and some other primates. Various monkeys can be experimentally infected by the virus is injected directly into the spinal cord or the brain. Only chimpanzees and Old World monkeys may also like humans are infected by the oral route. Since the virus for infection a specific receptor, the CD155 protein is needed on the host cells, the infection of an organism depends largely on whether the virus can bind to the receptor in the host. The poliovirus binds to CD155 of man, the chimpanzees and Old World monkeys, but only partly to CD155 of new world monkeys. After binding to the CD155 receptor, the virus is taken up into the cell where it can replicate. The propagation mechanisms within the cell are less host-specific than the uptake mechanism. The CD155 receptor located on the cell surface of monocytes, macrophages, T- lymphocytes and neurons. Lymphatic tissues such as the Peyer's patches in the intestine are the site of the first virus.

Disease detection and vaccines

Disease

After the virus was absorbed from the mouth, and has increased in the rhinopharynx, and in the intestinal tract, there is a viremia, in which the virus is distributed via the blood stream. In most cases, this goes without any symptoms; only in 4-8 % of those infected it comes to flu-like symptoms.

Only in rare cases, at around 1 % of infections, the viruses infect nerve cells, preferably of interest to the muscles of the anterior horn cells in the spinal cord. This then leads to the clinical picture of poliomyelitis.

Proof

The detection of the virus can occur from stool samples, throat swabs and possibly from cerebrospinal fluid. In the classical virological evidence, the treated material is incubated in cell cultures and determined the identity of the virus with a neutralization test with specific antisera. Isolation of the virus from stool samples to be successful in the first 14 days of the disease to 80%. This methodology is complex. Therefore, today the reverse transcriptase - polymerase chain reaction is often used, can be detected in clinical material with the right viral RNA. Sometimes even parts of the viral genome to be sequenced to produce on sequence comparisons, correlations between different patients and to be able to trace the route of infection. A detection of antibodies against the virus in the serum of the patients can be performed.

A proof of the polio virus is notifiable under the German Infection Protection Act.

Vaccines

There are two different polio vaccines. The inactivated polio vaccine ( IPV) by Jonas E. Salk is an inactivated vaccine that is injected intramuscularly. The vaccine contains cell culture grown, inactivated with formaldehyde virus particles of the three types. This vaccine provides good protection against the disease; the key benefit of this vaccine is that a vaccine Poliomyelitis is excluded. The inactivated polio vaccine was approved in the U.S. in 1955 and led there to a rapid decline of the disease.

The oral polio vaccine ( OPV) by Albert Sabin for oral vaccination is a live vaccine and consists of a mixture of the three types of so-called attenuated viruses that are still capable of reproduction, but excite no more disease. The advantage of this vaccine in addition to the ease of use in that it also generates an immunity in the gastrointestinal tract, which prevents not only the disease but also a transmission of the virus. In Germany, this vaccine is no longer used as a vaccine poliomyelitis can not be completely excluded. As the polio virus is eradicated in Germany, this would be an unacceptable risk.