Rotavirus infection: causes and pathogenesis

Causes of rotavirus infection

The cause of rotavirus infection is a representative of the family Reoviridae, the genus Rotavirus. The name is based on the morphological similarity of rotaviruses to the wheel (from the Latin "rota" - "wheel"). Under the electron microscope, the viral particles look like wheels with a wide hub, short spokes and a clearly defined thin rim. The rotavirus virion with a diameter of 65-75 nm consists of an electron-dense center (core) and two peptide envelopes: the outer and inner capsids. The core of 38-40 nm in diameter contains internal proteins and a genetic material represented by double-stranded RNA. The genome of human and animal rotaviruses consists of 11 fragments, which is probably due to the antigenic variety of rotaviruses. Replication of rotaviruses in the human body occurs exclusively in the epithelial cells of the small intestine.

In the composition of rotaviruses, four major antigens were found; the main one is the group antigen - the protein of the inner capsid. Taking into account all group-specific antigens, rotaviruses are divided into seven groups: A, B, C, D, E, F, G. Most human and animal rotaviruses belong to group A, within which subgroups (I and II) and serotypes are isolated. Subgroup II includes up to 70-80% of strains isolated from patients. There are data on the possible correlation of certain serotypes with the severity of diarrhea.

Rotaviruses are resistant to environmental factors: in drinking water, open water and sewage, they persist for up to several months, on vegetables - 25-30 days, on cotton, wool - up to 15-45 days. Rotaviruses are not destroyed by repeated freezing, under the influence of disinfectant solutions, ether, chloroform, ultrasound, but die by boiling. Treatment with solutions with a pH greater than 10 or less than 2. Optimal conditions for the existence of viruses: 4 ° C and high (> 90%) or low (<13%) humidity. Infectious activity increases with the addition of proteolytic enzymes (eg, trypsin, pancreatin).

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

The pathogenesis of rotavirus infection

The pathogenesis of rotavirus infection is complicated. On the one hand, the structural (VP3, VP4, VP6, VP7) and nonstructural (NSP1, NSP2, NSP3, NSP4, NSP5) proteins of the virus attach great importance to the development of rotavirus gastroenteritis . In particular, NSP4-peptide is an enterotoxin that causes secretory diarrhea, similar to bacterial toxins; NSP3 affects the replication of the virus, and NSP1 can "prohibit" the production of interferon-regulating factor 3.

On the other hand, already in the first day of the disease, rotavirus is found in the epithelium of the duodenal mucosa and the upper parts of the jejunum, where it multiplies and accumulates. Penetration of rotavirus into the cell is a multi-stage process. For introduction into the cell, some rotovirus serotypes need specific receptors containing sialic acid. The important role of proteins: a2b1-integrin, integrin-aVb3 and hsc70 at the initial stages of interaction of the virus and the cell, while the whole process is controlled by the VP4 virus protein . Penetrating the cells inside, the rotaviruses cause the death of the mature epitheliocytes of the small intestine and the rejection of them from the villi. Cells that replace the villous epithelium are functionally inferior and can not adequately absorb carbohydrates and simple sugars. The emergence of disaccharidic (mainly lactase) insufficiency leads to the accumulation in the intestine of uncleaved disaccharides with high osmotic activity, which causes a disruption of the reabsorption of water, electrolytes and the development of watery diarrhea, often leading to dehydration. Entering the large intestine, these substances become substrates for fermentation by intestinal microflora with the formation of a large number of organic acids, carbon dioxide, methane and water. Intracellular metabolism of cyclic adenosine monophosphate and guanosine monophosphate in epithelial cells during this infection practically does not change.

Thus, at present two main components are distinguished in the development of diarrheal syndrome: osmotic and secretory.

Epidemiology of rotavirus infection

The main source and reservoir of rotavirus infection is a sick person, releasing a significant amount of viral particles with feces (up to 10 ¹⁰ CFU per 1 g) at the end of the incubation period and in the early days of the disease. After the 4th-5th day of illness, the amount of the virus in the bowel movement is significantly reduced, but the total duration of rotavirus release is 2-3 weeks. Viral particles are permanently isolated from patients with impaired immunological reactivity, with chronic concomitant pathology, lactase deficiency. The source of infection can also be healthy virus carriers (children from organized collectives and hospitals, adults: first of all, medical personnel of maternity hospitals, somatic and infectious departments), from the feces of which rotavirus can be isolated for several months.

The mechanism of transmission of the pathogen is fecal-oral. Transmission paths:

• contact-household (through dirty hands and household items);
• water (with the use of virus-infected water, including bottled water);
• alimentary (most often with milk, dairy products).

The possibility of an airborne pathway for the transmission of rotavirus infection is not excluded.

Rotavirus infection is highly contagious, as evidenced by the rapid spread of the disease in the environment of patients. During outbreaks, up to 70% of non-immune populations become ill. In the seroepidemiological study of blood, 90% of children of older age groups have antibodies to various rotaviruses.

After the transferred infection in most cases short type-specific immunity is formed. Possible repeated diseases. Especially in older age groups.

Rotavirus infection occurs ubiquitously and is found in all age groups. In the structure of acute intestinal infections, the proportion of rotavirus gastroenteritis varies from 9 to 73%. Depending on age, region, standard of living and season. Especially often children of the first years of life are ill (mainly from 6 months to 2 years). Rotaviruses - one of the causes of diarrhea, accompanied by severe dehydration in children under the age of 3 years, this infection is caused by up to 30-50% of all cases of diarrhea requiring hospitalization or intensive rehydration. According to WHO, from this disease in the world every year from 1 to 3 million children die. Rotavirus infection accounts for about 25% of cases of so-called travelers' diarrhea. In Russia, the incidence of rotavirus gastroenteritis in the structure of other acute intestinal infections varies from 7 to 35%. And among children under 3 years - more than 60%.

Rotaviruses are one of the most common causes of an intra-hospital infection. Especially among preterm infants and young children. In the structure of nosocomial acute intestinal infections, the share of rotaviruses falls from 9 to 49%. Long-term hospital stay contributes to hospital-acquired infection. Essential role in the transfer of rotaviruses is played by medical personnel: 20% of employees even have IgM antibodies to rotavirus in the absence of intestinal disorders in the serum, and rotavirus antigen is detected in co-filters.

In temperate climates, rotavirus infection is seasonal in nature, predominant in the cold winter months, which is associated with better virus survival in the environment at low temperatures. In tropical countries, the disease occurs all year round with a certain increase in the incidence in the cool rainy season.

[10], [11], [12], [13], [14], [15], [16], [17], [18], [19], [20],