Respiratory adenoviruses

The first representatives of the family of adenoviruses were isolated in 1953 by W. Rowe (and others) from the tonsils and adenoids of children, in connection with which they received this name. The family Adenoviridae is divided into two genera: Mastadenovirus - adenoviruses of mammals, it includes human adenoviruses (41 serovariants), monkeys (24 sevoravianta), as well as cattle, horses, sheep, pigs, dogs, mice, amphibians; and Aviadenovirus - avian adenoviruses (9 serovariants).

Adenoviruses are devoid of supercapsid. The virion has the shape of an icosahedron - a cubic type of symmetry, its diameter is 70-90 nm. The capsid consists of 252 capsomers with a diameter of 7-9 nm. Groups of 9 capsomers form 20 equilateral facets (180 capsomers), and at their corners 12 vertices consisting of 6 capsomers (72 capsomers) are located. Since each of the 180 capsomers is adjacent to six others, it is called a hexon. In turn, the hexon consists of three subunits with a mass of 120 kD. Each of the 12 vertex capsomers is adjacent to five, so it is called a pentone. Twelve vertex icosahedron capsomers carry filamentous protuberances (fibers) 8-30 nm in length, terminating in a 4-nm diameter head. In the core of the virion, there is a deoxyribonucleoprotein consisting of a double-stranded genomic DNA molecule (20-25 MD), with a terminal protein (55 kD) covalently bound to the 5-ends of both strands, and two major proteins: VII (18 kD) and V (48 kD). The deoxyribonucleoprotein is a structure of 12 loops whose vertices are directed toward the bases of the vertex capsids, so the virion core on the cut is in the form of a flower. On the outer surface there is protein V. In addition, in the core there are proteins VI and X. The genome of adenoviruses is represented by double-stranded linear DNA with a mass of 19-24 MD. DNA strands are flanked by terminal inverted repeats, allowing the formation of ring molecules. With the 5 'ends of both strands, a hydrophobic terminal protein is covalently linked, which is necessary for the initiation of DNA replication. The number of genes in the DNA molecule is not exactly established. In human adenoviruses, the proportion of proteins is 86-88% of the mass of the virion. The total number of them is probably more than 30, and the micrometer varies from 5 to 120 kD. Proteins are denoted by Roman numerals, are characterized from them II-XIII. Currently, four areas of early transcription E1, E2, E3, E4 and at least 5 later regions - LI, L2, L3, L4, L5 have been identified in the genome of adenoviruses.

E1 products inhibit the transport of cellular mRNA to the cytoplasm and their translation. The E2 region encodes the synthesis of a DNA-binding protein, which plays an important role in the replication of viral DNA, the expression of early genes, in the control of splicing and the assembly of virions. One of the late proteins protects adenoviruses from the action of interferon. Among the main products encoded by late genes are proteins that form hexons, pentons, the core of the virion, and a non-structural protein that performs three functions: a) participates in the formation of hexon trimers; b) carries out transportation of these trimers to the core; c) participates in the formation of adenovirus mature virions. At least 7 antigens were detected in the virion. Antigen A (hexone) is group-specific and common for all human adenoviruses. For antigen B (pentone base), all human adenoviruses are divided into three subgroups. Antigen C (filaments, fibers) is type-specific. According to this antigen, all human adenoviruses are divided into 41 serovariants. All human adenoviruses, except for serovarians 12,18 and 31, have hemagglutinating activity, which is mediated by penton (apical capsomer). To identify the serovarians of adenoviruses, L. Rosen in 1960 proposed the RTGA.

The life cycle of adenoviruses with a productive infection consists of the following stages:

• adsorption on specific receptors of the cell membrane with the help of the head of fibers;
• penetration into the cell by the mechanism of receptor-mediated endocytosis, accompanied by partial "stripping" in the cytoplasm;
• the final deproteinization of the genome in the nuclear membrane and its penetration into the nucleus;
• synthesis of early mRNAs using cellular RNA polymerase;
• synthesis of early virus-specific proteins;
• replication of genomic viral DNA;
• synthesis of late mRNA;
• synthesis of late viral proteins;
• morphogenesis of virions and their exit from the cell.

Transcription and replication processes occur in the nucleus, the translation process in the cytoplasm, where the proteins are transported to the nucleus. The morphogenesis of virions also occurs in the nucleus and is of a multistage nature: first, the polypeptides are assembled into multimeric structures - fibers and hexons, then capsids, immature virions and finally mature virions are formed. In the nuclei of infected cells, virions often form crystalline clusters. In the late stages of infection, not only mature virions accumulate in the nuclei, but also immature capsids (without DNA). The yield of newly synthesized virions is accompanied by cell destruction. Out of a cell in which up to a million new virions are synthesized, not all of them come out. The remaining virions disrupt the functions of the nucleus and cause degeneration of the cells.

In addition to the productive form of infection, adenoviruses can cause abortifacient infection, in which reproduction of the virus is severely impaired at an early or later stage. In addition, some serovariants of human adenoviruses are capable of inducing malignant tumors by inoculation to various rodents. According to their oncogenic properties, adenoviruses are divided into highly ionogenic, weakly oncogenic and non-oncogenic. Oncogenic abilities are inversely related to the content of G-C pairs in the DNA of adenoviruses. The main event that leads to the transformation of cells (including in their cultures) is the integration of viral DNA into the chromosome of the host cell. Molecular mechanisms of the oncogenic effect of adenoviruses remain unclear.

Oncogenic properties in relation to human adenoviruses do not possess.

Adenoviruses do not reproduce in chick embryos, but they multiply well in primary-trypsinized and transplantable cell cultures of various origins, causing a characteristic cytopathic effect (rounding of cells and the formation of clusters of them, small-point degeneration).

Compared to other human viruses, adenoviruses are somewhat more stable in the external environment, they are not destroyed by fat solvents (there are no lipids), they do not die at a temperature of 50 ° C and at a pH of 5.0-9.0; well preserved in the frozen state.

Features of epidemiology. The source of infection is only a sick person, including a hidden form. Infection occurs by airborne, by contact-household way, through water in swimming pools and fecal-oral route. In the intestine, the virus can penetrate through the blood. Diseases of the upper respiratory tract and eyes cause serovariants 1-8,11,19,21. Serovariants 1, 2, 3, 12, 18, 31, 40 and 41 cause gastroenteritis in children from 6 months. Up to 2 years, mesenteric adenitis. Serovariants 1, 2, 5, 6 are often found with latent forms of infection.

There is no data on the ability of animal adenoviruses to cause disease in humans, and conversely, human adenoviruses - in animals. Adenoviruses cause sporadic diseases and local epidemic outbreaks. The largest outbreak in our country was 6000 people.

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Symptoms of adenovirus infection

The incubation period is 6-9 days. The virus multiplies in the epithelial cells of the upper respiratory tract, the mucous membrane of the eyes. Can penetrate into the lungs, affect bronchi and alveoli, cause severe pneumonia; the characteristic biological property of adenoviruses is tropism to the lymphoid tissue.

Adenoviral diseases can be characterized as febrile with catarrhal inflammation of the mucous membrane of the respiratory tract and eyes, accompanied by an increase in submucous lymphoid tissue and regional lymph nodes. Most often they occur in the form of tonsillitis, pharyngitis, bronchitis, atypical pneumonia, influenza-like disease, in the form of pharyngo-conjunctival fever. Conjunctivitis in some cases accompanies adenoviral disease, in others - the main symptom of it.

Thus, adenoviral diseases are characterized by a predominance of respiratory, conjunctival or intestinal syndrome. At the same time, the virus can cause a latent (asymptomatic) or chronic infection with long persistence in the tissues of the tonsils and adenoids.

Postinfectious immunity is long-lasting, resistant, but type-specific, there is no cross immunity. Immunity is caused by virus-neutralizing antibodies and immune memory cells.

Laboratory diagnosis of adenovirus infection

1. Detection of viral antigens in the affected cells using immunofluorescence or IFM.
2. Isolation of the virus. The material for the study is a detachable nasopharynx and conjunctiva, blood, excrement (the virus can be identified not only at the beginning of the disease, but also on the 7th-14th day). To isolate the virus, primary-trypsinized cells (including diploid) cell cultures of the human embryo are used, which are sensitive to all adenovirus serovariants. Viruses are detected by their cytopathic effect and by the use of RSK, since they all have a common complement-binding antigen. Identification is carried out by type-specific antigens with the help of RTGA and PH in the cell culture.
3. Detection of the growth of antibody titer in paired sera of a patient with the help of DSC. Determination of the growth of titer of type-specific antibodies is performed with reference adenovirus serostamms in RTGA or PH in the cell culture.

Specific prophylaxis of adenovirus infection

Against some adovovirus serovariants, living immunogenic oral vaccines were obtained, but they were not widely used.