Respiratory adenoviruses

The first representatives of the adenovirus family were isolated in 1953 by W. Rowe (et al.) from the tonsils and adenoids of children, which is why they received this name. The Adenoviridae family is divided into two genera: Mastadenovirus - mammalian adenoviruses, it includes adenoviruses of humans (41 serovariants), monkeys (24 serovariants), as well as cattle, horses, sheep, pigs, dogs, mice, amphibians; and Aviadenovirus - bird adenoviruses (9 serovariants).

Adenoviruses lack a 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 capsomeres with a diameter of 7-9 nm. Groups of 9 capsomeres form 20 equilateral faces (180 capsomeres), and at their corners there are 12 vertices consisting of 6 capsomeres (72 capsomeres). Since each of the 180 capsomeres is adjacent to six others, it is called a hexon. In turn, a hexon consists of three subunits with m.m. 120 kD. Each of the 12 vertex capsomeres is adjacent to five, so it is called a penton. Twelve vertex capsomeres of the icosahedron carry filamentous protrusions (fibers) 8-30 nm long, ending with a head 4 nm in diameter. The core of the virion contains deoxyribonucleoprotein consisting of a double-stranded genomic DNA molecule (20-25 MD), with a terminal protein (55 kD) covalently linked to the 5' ends of both strands, and two main proteins: VII (18 kD) and V (48 kD). Deoxyribonucleoprotein is a structure of 12 loops, the apices of which are directed toward the bases of the apical capsids, so the virion core has a flower-shaped cross-section. Protein V is located on the outer surface. In addition, proteins VI and X are located in the core. The adenovirus genome is represented by double-stranded linear DNA with m.m. 19-24 MD. DNA strands are flanked by terminal inverted repeats, which allow the formation of ring molecules. A hydrophobic terminal protein, which is necessary for the initiation of DNA replication, is covalently linked to the 5' ends of both strands. The number of genes in a DNA molecule has not been precisely determined. In human adenoviruses, proteins account for 86-88% of the virion mass. Their total number is probably more than 30, and m. m. varies from 5 to 120 kD. Proteins are designated by Roman numerals, of which II-XIII have been characterized. At present, four regions of early transcription E1, E2, E3, E4 and at least 5 regions of late transcription - LI, L2, L3, L4, L5 have been identified in the adenovirus genome.

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

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

• adsorption on specific receptors of the cell membrane using the fiber head;
• penetration into the cell by means of the mechanism of receptor-mediated endocytosis, accompanied by partial "undressing" in the cytoplasm;
• final deproteinization of the genome at 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 mRNAs;
• synthesis of late viral proteins;
• morphogenesis of virions and their exit from the cell.

The processes of transcription and replication occur in the nucleus, the process of translation - in the cytoplasm, from where proteins are transported to the nucleus. The morphogenesis of virions also occurs in the nucleus and is multistage: first, 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 but also immature capsids (without DNA) accumulate in the nuclei. The release of newly synthesized virions is accompanied by the destruction of cells. Not all of them leave the cell in which up to a million new virions are synthesized. The remaining virions disrupt the functions of the nucleus and cause cell degeneration.

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

Adenoviruses do not have oncogenic properties in relation to humans.

Adenoviruses do not reproduce in chicken embryos, but reproduce well in primary trypsinized and transplanted cell cultures of various origins, causing a characteristic cytopathic effect (rounding of cells and formation of grape-like clusters, fine-point degeneration).

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

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

There is no data on the ability of animal adenoviruses to cause diseases in humans, and, conversely, human adenoviruses - in animals. Adenoviruses cause sporadic diseases and local epidemic outbreaks. The largest outbreak in our country affected 6,000 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. It can penetrate the lungs, affect the bronchi and alveoli, and cause severe pneumonia; a characteristic biological property of adenoviruses is tropism to 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 submucosal lymphoid tissue and regional lymph nodes. Most often, they occur in the form of tonsillitis, pharyngitis, bronchitis, atypical pneumonia, flu-like disease, in the form of pharyngoconjunctival fever. Conjunctivitis in some cases accompanies adenoviral disease, in others - its main symptom.

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

Post-infection immunity is long-lasting, stable, but type-specific, there is no cross-immunity. Immunity is due to virus-neutralizing antibodies and immune memory cells.

Laboratory diagnostics of adenovirus infection

1. Detection of viral antigens in affected cells using immunofluorescence or IFM methods.
2. Isolation of the virus. The material for the study is nasopharyngeal and conjunctival secretions, blood, and feces (the virus can be isolated not only at the onset of the disease, but also on the 7th to 14th day). Primary trypsinized cell cultures (including diploid) of the human embryo, which are sensitive to all serotypes of adenoviruses, are used to isolate the virus. Viruses are detected by their cytopathic effect and by means of the complement-binding antigen (CBA), since they all have a common complement-binding antigen. Identification is performed by type-specific antigens using the RTGA and RN in the cell culture.
3. Detection of the increase in the antibody titer in paired patient sera using the RSC. The determination of the increase in the titer of type-specific antibodies is carried out with standard adenovirus serostrains in RTGA or RN in cell culture.

Specific prevention of adenovirus infection

Live immunogenic oral vaccines have been developed against some adenovirus serovariants, but they have not been widely used.