Rabdoviruses - pathogens of rabies and vesicular stomatitis

Rabies - an acute infectious disease caused by a rhabdovirus - occurs when a person bites a sick animal or when it comes to the damaged skin or mucous membrane of the saliva of a sick animal. This infection of the central nervous system almost always ends up lethal.

The first mention of a disease transmitted through a dog's bite and very similar to rabies described in the description is found in the cuneiform clay tablets of Ancient Mesopotamia dating back to the 3rd millennium BC. E. The virus was isolated and attenuated by passages on the rabbit's brain in 1882 by I. Pasteur.

Vesicular stomatitis - a disease of horses, cattle and pigs, sometimes people, flowing in them benignly - is also caused by a rhabdovirus. For humans, this virus is slightly pathogenic. It is studied better than all the rabdoviruses.

[1], [2], [3], [4]

Life cycle

Rabdoviruses are a family in which there are 3 genera: Vesiculovirus (10 mammalian viruses, typical virus of vesicular stomatitis, or Air Force); yssavirus (6 serologically related viruses, typical - rabies virus); Sigmavirus (the only representative is the sigma-drosofil virus). Unclassified are 6 viruses that cause fish diseases, and 13 viruses that damage plants. Rhabdoviruses are characterized by a rod-shaped or bullet-shaped virion: a length of 60-400 nm, a width of 60-85 nm. The particles are surrounded by a two-layer lipid membrane-like shell with protruding spines 10 nm long and 3 nm wide. Under the membrane is ribonucleocapsid, which has a spiral type of symmetry, in which electron bands are visible. The genome of rhabdoviruses is represented by a negative single-stranded linear unfragmented RNA molecule with a molecular weight of 3.8 MD; Five genes encoding the synthesis of structural proteins were found and the order of their location was determined. The nucleocapsid protein N (50 kD) gene is located at the 3 'end. It is followed by the NSV protein gene (30 kD), one of the components of the viral transcriptase, which is part of the nucleocapsid. The following gene encodes the matrix protein M (30 kD) and the lining of the bilayer lipid membrane from the inside. Yes, there is a gene for protein G (65 kD), an external glycoprotein of the virus supercapsid. At the 5'-end there is a gene of the high-molecular component of the viral transcriptase - protein L (160 kD).

The interaction of the rhabdoviruses with the cells and their reproduction proceed according to the following scheme: the adsorption of the virus on the cell (glycoprotein G) - penetration into the cell by endocytosis - fusion with the lysosome membrane - deproteinization of the virus. Under the action of the virion transcriptase (RNA polymerase), cRNA is formed, serving as a template for the synthesis of vRNA and performing the mRNA function. Further, virus-specific proteins are synthesized on the ribosomes of the host cell. The proteins M and G are inserted into the plasma membrane. Formed by the interaction of vRNA with proteins N, L and NS nucleocapsid, passing through the membrane, enveloped by a super-capsid. The ripened virion is separated from the cell by budding.

The rabies virus in the structure and features of intracellular reproduction is very similar to the virus of vesicular stomatitis. An important feature of these viruses is the pronounced inhibition of protein biosynthesis in the host cell by blocking the initiation of translation. There are several serovariants of vesicular stomatitis viruses, which differ in the protein G, which is also a protective antigen.

Viruses multiply well in chick embryos, kidney cells of newborn hamsters and in cultures of human diploid cells. In cell cultures, the virus of vesicular stomatitis usually causes a cytopathic effect and cell death, sometimes a symplast formation.

The rabies virus has a wide range of hosts. All warm-blooded animals are sensitive to it. The degree of pathogenicity of different strains of rabies viruses for different animals is not the same. In some species of bats, the virus adapted only to the salivary glands, without causing signs of disease; infection of other animals always leads to death.

Strains of rabies viruses circulating in nature in animals are called street strains. They cause diseases with a fairly long incubation period and usually form specific body-inclusions in the cytoplasm of cells. Infected animals can have a long period of excitement and aggression. The virus can penetrate into the salivary glands and the central nervous system. Consecutive passages in the brains of rabbits lead to the formation of a fixed virus that can not later reproduce in any cells other than the nervous ones. The fixed virus multiplies rapidly, the incubation period is short, inclusions in the cells are rarely detected. This virus is pathogenic only for rabbits.

The rabies virus is not very stable in the external environment, it is rapidly inactivated by the action of ultraviolet rays or sunlight on it. When boiling, it dies after 2 minutes, at 60 ° C - after 5 minutes. Quickly inactivated by solutions of lysol, chloramine, phenol, fat solvents and trypsin. In animal corpses, especially at low temperatures, it persists up to 4 months.

Immunity

Since the disease with rabies ends with death, postinfectious immunity has not been studied. It was established that antibodies can be formed during the disease and after vaccination. Postvaccinal immunity persists up to 1 year.

Epidemiology of rabies

Rabies is a typical zooanthroponosis. The main source and reservoir of the virus are wild and domestic carnivores: dogs, cats, wolves, jackals, foxes, skunks, mongooses, bats. The disease is usually transmitted through a bite or when the damaged skin or mucous membranes are inflamed, as the virus multiplies in the salivary glands of the animal. A sick animal is contagious not only during illness, but also in the incubation period for 2 to 3 days, sometimes more, before the appearance of the first signs of the disease.

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Symptoms of rabies

Primary reproduction of the rabies virus occurs in the muscle tissue near the entrance gates, then the pathogen is introduced into the receptors of the peripheral sensory nerves and through the endonus of the Schwann cells or through the perineural spaces enters the central nervous system. There, the virus multiplies in neurons of the hippocampus, oblong brain, cranial nerves, sympathetic ganglia, causing inflammatory, dystrophic and necrotic changes in the nervous system. During this period, the virus also multiplies in the cells of the salivary glands.

The shortest incubation period occurs with a bite of the head and hands, longer - with a bite of the lower limbs; in general, varies from 8 to 90 days. In the development of the disease, three stages are distinguished: precursors (depression), stimulation, paralysis. First there is anxiety, fear, anxiety, unpleasant sensations in the field of a bite. After 1-3 days, there is marked excitement, convulsions of the respiratory and swallowing muscles, there is a pronounced hydrophobia (hydrophobia is the second name of this disease). During this period, aggressiveness, auditory and visual hallucinations are characteristic. Then the paralysis develops, and in 5-7 days after the onset of the disease death from paralysis of the heart or respiratory center occurs.

Laboratory diagnostics of rabies

Diagnosis of rabies is carried out using viroscopic, biological and serological methods. In dead animals and people in histological sections or smears-prints, brain tissue (cortex of the cerebral hemispheres and cerebellum, ammon horn, medulla oblongata) and tissue of the salivary glands are examined. In the pyramidal cells of the brain tissue, specific eosinophilic inclusions (Babesh-Negri bodies) are located in the cytoplasm near the nucleus and are clusters of viral nucleocapsids. Their appearance is due to the difficult maturation of virions in nerve cells. The Babes-Negri Taurus is revealed by special methods of coloring (Romanovsky-Giemsa, Mannu, Turevich, Muromtsev, etc.). They have a characteristic granular structure with basophilic granules on the acidophilic background, their size is 4-10 μm. The disadvantage of the method is that it can be used only after the death of a person or animal.

Viral antigen can be detected in the same preparations by direct or indirect immunofluorescence reaction.

The rabies virus can be isolated from the saliva of sick people or animals, as well as from fresh sectional material (brain tissue, submandibular salivary gland tissue) by intracerebral infection of white mice and rabbits or hamsters by intramuscular injection. In animals, paralysis develops with subsequent death. The brain of the deceased animal should be examined for the detection of Babes-Negri calves or viral antigen by the immunofluorescence reaction.

Antibodies can be detected in vaccinated individuals by neutralization reactions, complement fixation, immunofluorescence, and immunosorbent reactions (RIM and IFM).

Specific prophylaxis and treatment of rabies

Prevention of rabies is to combat rabies in animals and prevent the development of the disease in people who have been bitten or maimed by sick animals. The program for the elimination of rabies in terrestrial animals must be considered in two aspects:

1. eradication of urban canine rabies and
2. improvement of natural foci of rabies infection.

The experience of many countries convincingly proves the possibility of controlling urban epizootics by registering and immunizing dogs. However, for the complete elimination of the rabic infection, it is necessary to improve its natural foci, and the extermination of wild carnivores gives only a temporary and local result and threatens the development of undesirable environmental consequences. Abroad, there is already a large positive experience of preventing rabies among wild animals (foxes, raccoons) by feeding them baits containing the vaccine. Very promising in this regard are oral anti-rabies vaccines: a live modified whole-virion vaccine from attenuated vaccine strains (SAD-Bern, Vnukovo-32) and a recombinant genetically engineered oral vaccine using the vaccinia virus expressing the G protein gene of the rabies virus as a vector.

With bites or oslubneni it is necessary to thoroughly wash the wound or skin in the place where saliva comes in with soapy water, apply the alcohol solution of iodine to the wound and begin the specific prevention with rabies vaccine and rabies gamma globulin. Instead of the previously highly reactogenic Fermi vaccine (from the cerebral tissue of sheep infected with a fixed virus), an antirabic inactivated culture rabies vaccine is now recommended for the prevention of the disease , which is made on the culture of cells infected with an attenuated rabies virus (Vnukovo-32 strain). Emergency treatment and prophylactic vaccination is carried out by vaccine or vaccine in combination with rabies gamma-globulin according to the schemes indicated in the instructions for their use. The vaccination schedule is determined by the degree of severity of the bite, its location, the time passed after the bite, information about the bitten animal and other circumstances.