Influenza - Causes and Pathogenesis

Causes of flu

The cause of influenza is orthomyxoviruses (Orthomyxoviridae family) - RNA-containing complex viruses. They got their name due to their affinity for mucoproteins of affected cells and the ability to attach to glycoproteins - cell surface receptors. The family includes the genus Influenzavirus, which contains viruses of 3 serotypes: A, B and C.

The diameter of the viral particle is 80-120 nm. The virion is spherical (less often filiform). The nucleocapsid is located in the center of the virion. The genome is represented by a single-stranded RNA molecule, which has 8 segments in serotypes A and B and 7 segments in serotype C.

The capsid consists of a nucleoprotein (NP) and polymerase complex proteins (P). The nucleocapsid is surrounded by a layer of matrix and membrane proteins (M). Outside these structures is an outer lipoprotein membrane that carries complex proteins (glycoproteins) on its surface: hemagglutinin (H) and neuraminidase (N).

Thus, influenza viruses have internal and surface antigens. Internal antigens are represented by NP and M proteins; these are type-specific antigens. Antibodies to internal antigens do not have a significant protective effect. Surface antigens - hemagglutinin and neuraminidase - determine the subtype of the virus and induce the production of specific protective antibodies.

Serotype A viruses are characterized by constant variability of surface antigens, with changes in H- and N-antigens occurring independently of each other. There are 15 known subtypes of hemagglutinin and 9 of neuraminidase. Serotype B viruses are more stable (there are 5 subtypes). The antigenic structure of serotype C viruses is not subject to change; they lack neuraminidase.

The extraordinary variability of serotype A viruses is due to two processes: antigenic drift (point mutations in genome sites that do not go beyond the strain) and shift (complete change in the structure of the antigen with the formation of a new strain). The cause of antigenic shift is the replacement of an entire RNA segment as a result of the exchange of genetic material between human and animal influenza viruses.

According to the modern classification of influenza viruses proposed by WHO in 1980, it is customary to describe the serotype of the virus, its origin, year of isolation and subtype of surface antigens. For example: influenza virus A, Moscow/10/99/NZ N2.

Serotype A viruses have the highest virulence and are of the greatest epidemiological significance. They are isolated from humans, animals and birds. Serotype B viruses are isolated only from humans: in terms of virulence and epidemiological significance, they are inferior to serotype A viruses. Influenza C viruses are characterized by low reproductive activity.

In the environment, the resistance of viruses is average. They are sensitive to high temperatures (over 60 °C), ultraviolet radiation and fat solvents, but they retain virulent properties for some time at low temperatures (they do not die at a temperature of 40 °C for a week). They are sensitive to standard disinfectants.

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Pathogenesis of influenza

The influenza virus has epitheliotropic properties. When it enters the body, it reproduces in the cytoplasm of the columnar epithelium cells of the respiratory tract mucosa. Virus replication occurs quickly, within 4-6 hours, which explains the short incubation period. Cells affected by the influenza virus degenerate, become necrotic and are rejected. Infected cells begin to produce and secrete interferon, which prevents further spread of the virus. Non-specific thermolabile B-inhibitors and secretory antibodies of the IgA class contribute to the body's protection from viruses. Metaplasia of the columnar epithelium reduces its protective function. The pathological process affects the tissues lining the mucous membranes and the vascular network. The epitheliotropism of the influenza virus is clinically expressed as tracheitis, but the lesion can affect large bronchi, sometimes the larynx or pharynx. Viremia is already expressed in the incubation period and lasts for about 2 days. Clinical manifestations of viremia are toxic and toxic-allergic reactions. Such an effect is exerted by both viral particles and the products of epithelial cell decay. Intoxication in influenza is primarily due to the accumulation of endogenous biologically active substances (prostaglandin E2, serotonin, histamine). The role of free oxygen radicals that support the inflammatory process, lysosomal enzymes, as well as the proteolytic activity of viruses in the implementation of their pathogenic effect has been established.

The main link in pathogenesis is damage to the circulatory system. The vessels of the microcirculatory bed are most susceptible to changes. Due to the toxic effect of the influenza virus and its components on the vascular wall, its permeability increases, which causes hemorrhagic syndrome in patients. Increased vascular permeability and increased "fragility" of vessels lead to edema of the mucous membrane of the respiratory tract and lung tissue, multiple hemorrhages in the alveoli and interstitium of the lungs, as well as in almost all internal organs.

In case of intoxication and the resulting pulmonary ventilation disorders and hypoxemia, microcirculation is disrupted: the venulo-capillary blood flow rate slows down, the ability of erythrocytes and thrombocytes to aggregate increases, vascular permeability increases, the fibrinolytic activity of blood serum decreases, and blood viscosity increases. All this can lead to disseminated intravascular coagulation, an important link in the pathogenesis of infectious-toxic shock. Hemodynamic disorders, microcirculation, and hypoxia contribute to the occurrence of dystrophic changes in the myocardium.

Circulation disorders caused by vascular damage play an important role in damaging the functions of the central nervous system and the autonomic nervous system. The effect of the virus on the receptors of the vascular plexus contributes to hypersecretion of cerebrospinal fluid, intracranial hypertension, circulatory disorders, and cerebral edema. High vascularization in the hypothalamus and pituitary gland, which carry out neurovegetative, neuroendocrine, and neurohumoral regulation, causes the development of a complex of functional disorders of the nervous system. In the acute period of the disease, sympathicotonia occurs, leading to the development of hyperthermia, dryness and pallor of the skin, increased heart rate, and increased blood pressure. With a decrease in toxicosis, signs of excitation of the parasympathetic division of the autonomic nervous system are noted: lethargy, drowsiness, decreased body temperature, decreased pulse rate, drop in blood pressure, muscle weakness, adynamia (asthenovegetative syndrome).

A significant role in the pathogenesis of influenza and its complications, as well as in the development of inflammatory changes in the respiratory tract, belongs to bacterial microflora, the activation of which contributes to damage to the epithelium and the development of immunosuppression. Allergic reactions to influenza occur to antigens of both the virus itself and bacterial microflora, as well as to the decay products of affected cells.

The severity of influenza is partly determined by the virulence of the influenza virus, but to a greater extent by the state of the host's immune system.