The virus of poliomyelitis

The genome of the poliomyelitis virus is a single-stranded unfragmented RNA, consisting of 7.5-8 thousand nucleotides, its molecular weight is 2.5 MD. The organization of virion RNA has the following features that determine the nature of its behavior in the cell:

• coding sequences account for about 90% of the total length;
• between the 5'-end and the beginning of the reading frame is the so-called 5'-untranslated region, which accounts for about 10% of the length of the RNA; in this region there are from 6 to 12 AUG initiator codons;
• the genomic RNA of the poliovirus at the 5'-end does not contain a cap (cap); instead, a small virus-specific glycoprotein is covalently linked to the 5'-end of the RNA, which is cleaved by the cellular enzyme before translation;
• under the influence of virion RNA, the synthesis of protein factors necessary for the initiation of capped translation is suppressed in the cell, as a result of which the cap-independent translation of viral proteins is very active;
• in the 5-untranslated region of the poliovirus RNA, there is a special regulatory element that ensures its cap-independent translation. A relationship between the virus' s neurovirulence and the degree of activity of this Regulatory element is established, which determines the intensity of the synthesis of viral proteins, especially in nerve cells.

The mass of the virion is 8-9 MD. The virus has a spherical shape. The type of symmetry is cubic. The virion capsid is formed by four proteins of 60 copies each. Three of them - VP1, VP2, VP3 - form the outer surface of the capsid, and VP4 - the internal one, so it is not visible from the outside.

The virion shell is formed from 12 compact structures called pentamers, since they contain 5 molecules of each protein. Pentamers are arranged like a mountain, the top of which occupies VP1, and its base forms VP4; the VP2 and VP3 proteins intersect the footsteps. The virion genome is very tightly enclosed in its central cavity. Shell proteins play a role in recognizing the receptor of the host cell, in attaching the virion to it and in the release of the virion RNA within the cell. The virion does not possess hemagglutinating properties. The ability of the poliovirus to cause paralysis also appears to be associated with one of the envelope proteins. They are proteins, they determine the immunogenic properties of the virus. According to antigenic signs, polioviruses are divided into three types: I, II, III.

The greatest pathogenicity for humans is poliovirus type I: all significant poliomyelitis epidemics were caused by this type. Poliovirus type III causes epidemics less often. Poliovirus type II often causes a latent form of infection.

Intracellular multiplication of the virus. The interaction of the virus with the cell consists of the following stages:

• adsorption of the virus;
• penetration into the cell, accompanied by the destruction of the capsid and the release of genomic RNA.

Being positive, vRNA is directly translated into virus-specific proteins. One of these proteins, non-structural, is RNA replicase, with the participation of which the vRNA replication takes place according to the scheme:

VRNA -> cRNA -> vRNA.

Structural proteins, all four, are synthesized as the initial single polypeptide chain, which is then subjected to cascade proteolysis and is eventually cleaved into four VP1-VP4 proteins. This cutting, apparently, is catalyzed by the viral protein itself, it is necessary for the formation of newly formed virions. The newly synthesized vRNA is included in the capsid, and the formation of the virion ends here. The newly synthesized virions come out of the cell. From one virion, up to 150,000 virions are synthesized in the cell.

The word poliomyelitis (poliomyelitis) translated into Russian means inflammation of the gray matter of the brain (Greek polios - gray, myelitis - inflammation of the spinal cord). The fact is that the most important biological property of polioviruses is their tropism to the nervous tissue, they affect the motor cells of the gray matter of the spinal cord.

Pathogenesis and symptoms of poliomyelitis

The entrance gates for poliomyelitis is the mucous membrane of the pharynx, stomach and intestines. In them, the primary multiplication of the virus occurs, and therefore a few days after infection it can be found in pharyngeal mucus and feces. After reproduction in epithelial cells, the virus enters the regional lymph nodes, and then into the blood. In other words, following the alimentary stage of the disease, viremia begins with hematogenous dissemination of the pathogen. Symptoms of poliomyelitis in these two stages, as a rule, are absent. Only sometimes the virusemia is accompanied by a short-term fever and slight malaise, this characterizes the so-called "small" disease, it ends with recovery and the formation of post-infection immunity. However, polioviruses can overcome the blood-brain barrier and penetrate into the central nervous system, resulting in the development of a "big" disease. The viral death of motor neurons of the anterior horns of the spinal cord leads to the development of paralysis of skeletal muscles, as a result of which the patient either dies or remains disabled for life.

There are four main clinical forms of poliomyelitis:

• abortive (small disease);
• nonparalytic (meningeal), manifested by serous meningitis;
• paralytic;
• Inactive (hidden).

The paralytic form, depending on the localization of the focus, is divided into the spinal, bulbar, pontine (variolic bridge) and other, more rare forms.

The form of the flow of poliomyelitis is determined by the magnitude of the infectious dose, the degree of neurovirulence of the virus and the immune status of the organism. Foci of lesion are found in the anterior horns of the spinal cord, most often in the lumbar extension, in the motor cells of the reticular formation of the medulla oblongata and the variola bridge, the cerebellum, in the motor and premotor regions of the cerebral cortex.

Immunity with poliomyelitis

After the transferred disease (including latent form), there remains a lasting lifelong immunity caused by virus neutralizing antibodies and immune memory cells.

Epidemiology of poliomyelitis

The source of infection is only a person. Although the virus multiplies in the epithelial and lymphoid tissues of the upper respiratory tract, the airborne way of infection does not play an important role because of the absence of catarrhal phenomena. The main way of infection is fecal-oral. The virus is excreted in large quantities from the end of the incubation period (the last 3-7 days) to the 40th day of the disease, and in a number of cases, several months.

[1], [2], [3], [4], [5], [6], [7], [8], [9], [10],

Treatment of poliomyelitis

Treatment of acute poliomyelitis should be comprehensive and conducted taking into account the stage and form of the disease. In paralytic forms, it is especially important to observe the early orthopedic regimen. The main importance in the treatment of poliomyelitis belongs correctly and long-term gymnastics. Patients with respiratory disorders should be under the special supervision of specially trained personnel. Specific treatment of poliomyelitis is absent.

Specific prevention of poliomyelitis

Poliomyelitis by the middle of XX century. Turned into a formidable epidemic disease that periodically infect thousands and tens of thousands of people, of whom about 10% died, while 40% had lifelong paralysis. The only reliable weapon against this disease could be only a vaccine against poliomyelitis and the creation with its help of collective immunity. To do this, it was necessary to develop methods that would allow the virus to accumulate in the required amount. And the hard efforts of scientists finally gave their fruits. In the late 1940's and early 1950's. Methods have been developed for obtaining single-layer cell cultures (initially primary trypsinized, then transfused) that have been widely used to grow viruses, and there are real conditions for creating a vaccine against poliomyelitis. It should be noted that the development of methods for obtaining cell cultures was of great importance for the development of virology. In the 50's. XX century. Two poliomyelitis vaccines were created:

• Formalin-inactivated vaccine J. Salk.
• Live vaccine A. Sebina from attenuated strains of polioviruses I, II and III types.

Large-scale production of live vaccine was first mastered in the 1950s in our country. Immediately (since 1959), a massive vaccination of children against poliomyelitis with this vaccine was started. Both vaccines - dead and alive - are quite effective, but in our country a living vaccine is preferred, since vaccine strains, multiplying in the epithelial cells of the intestinal tract, are released into the external environment and circulating in collectives, displacing wild strains of polioviruses. On the recommendation of the WHO, vaccinations against poliomyelitis are mandatory and are carried out from 3 months of age and up to 16 years. Since a live vaccine, although extremely rare, causes complications, it is now recommended to inoculate vaccines with an inactivated Salk vaccine. With the help of available vaccines, the incidence of poliomyelitis in all countries of the world can and should be reduced to single cases, i.e., the opportunity to sharply reduce it.