Infectious mononucleosis - Causes and pathogenesis

Causes of infectious mononucleosis

The cause of infectious mononucleosis is the Epstein-Barr virus, which belongs to the herpes virus group (Herpesviridae family, Gammaherpesvirinae subfamily, Lymphocryptovirus genus), human herpes virus type 4. It contains DNA in the form of a double helix, which encodes more than 30 polypeptides. The virion consists of a capsid 120-150 nm in diameter, surrounded by a membrane containing lipids. The virion capsid has the shape of an icosahedron. EBV has a tropism for B-lymphocytes due to the presence of receptors for this virus on their surface. The virus can persist in the host cells for a long time in a latent form. It has antigenic components common with other herpes viruses. It is antigenically homogeneous and contains the following specific antigens: viral capsid antigen, nuclear antigen, early antigen, and membrane antigen. Viral antigens induce the production of antibodies - markers of EBV infection. Stability in the environment is low. The virus quickly dies when dried, under the influence of high temperatures (boiling, autoclaving), and treatment with all disinfectants.

Unlike other herpes viruses, the Epstein-Barr virus does not cause death, but proliferation of affected cells, therefore it is classified as an oncogenic virus, in particular, it is considered an etiologic factor of Burkitt's sarcoma, nasopharyngeal carcinoma, B-cell lymphoma, some immunodeficiencies, hairy leukoplakia of the tongue, and HIV infection. After primary infection, the Epstein-Barr virus persists in the body for life, integrating into the genome of affected cells. In case of disorders in the immune system and exposure to other factors, reactivation of the virus is possible.

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Pathogenesis of infectious mononucleosis

When the Epstein-Barr virus enters with saliva, the oropharynx serves as the gateway to infection and the site of its replication. The infection is supported by B-lymphocytes, which have surface receptors for the virus; they are considered the main target of the virus. Virus replication also occurs in the epithelium of the mucous membrane of the oropharynx and nasopharynx, and the ducts of the salivary glands. During the acute phase of the disease, specific viral antigens are found in the nuclei of more than 20% of circulating B-lymphocytes. After the infectious process subsides, viruses can be detected only in single B-lymphocytes and epithelial cells of the nasopharynx.

B-lymphocytes infected with the virus begin to proliferate intensively under the influence of viral mutagens, transforming into plasma cells. As a result of polyclonal stimulation of the B-system, the level of immunoglobulins in the blood increases, in particular, heterohemagglutinins appear, capable of agglutinating foreign erythrocytes (ram, horse), which are used for diagnostics. The proliferation of B-lymphocytes also leads to the activation of T-suppressors and natural killers. T-suppressors suppress the proliferation of B-lymphocytes. Their young forms appear in the blood, which are morphologically characterized as atypical mononuclears (cells with a large nucleus, like a lymphocyte, and wide basophilic cytoplasm). T-killers destroy infected B-lymphocytes by antibody-dependent cytolysis. Activation of T-suppressors leads to a decrease in the immunoregulatory index below 1.0, which facilitates the addition of a bacterial infection. Activation of the lymphatic system is manifested by an increase in lymph nodes, tonsils, other lymphoid formations of the pharynx, spleen and liver. Histologically, proliferation of lymphoid and reticular elements is detected, in the liver - periportal lymphoid infiltration. In severe cases, necrosis of lymphoid organs, the appearance of lymphoid infiltrates in the lungs, kidneys, central nervous system and other organs are possible.

Epidemiology of infectious mononucleosis

Infectious mononucleosis is an anthroponosis; the source of the infectious agent is a sick person, including those with an attenuated form of the disease, and a virus carrier. The epidemic process in the population is maintained by virus carriers, individuals infected with the Epstein-Barr virus, who periodically release the virus into the environment with saliva. The virus is detected in 15-25% of cases in oropharyngeal swabs of seropositive healthy individuals. When volunteers were infected with pharyngeal swabs of patients with infectious mononucleosis, distinct laboratory changes characteristic of EBV infectious mononucleosis (moderate leukocytosis, an increase in the number of mononuclear leukocytes, an increase in the activity of aminotransferases, heterohemagglutination) occurred; however, a full-blown clinical picture of mononucleosis was not observed in any case. The frequency of virus release increases sharply with disorders in the immune system. The main route of transmission is airborne. Infection is also possible through direct contact (kissing, sexual intercourse) and indirect contact through household items, toys contaminated with saliva containing the virus. Latent infection in B-lymphocytes of donors' peripheral blood creates a risk of infection during blood transfusions.

Humans are easily susceptible to the Epstein-Barr virus. The timing of primary infection depends on social and living conditions. In developing countries and socially disadvantaged families, most children are infected between the ages of 6 months and 3 years. Moreover, as a rule, the disease is asymptomatic; sometimes a picture of acute respiratory infections is observed. The entire population is infected by the age of 18. In developed countries and socially prosperous families, infection occurs at an older age. more often in adolescence or youth. By the age of 35, the majority of the population is infected. When infected at the age of over 3 years, 45% develop a typical picture of infectious mononucleosis. Immunity in those who have had infectious mononucleosis is lifelong, non-sterile, repeated diseases are not observed, but various manifestations of EBV infection are possible, caused by reactivation of the virus.

Males are more often affected. People over 40 years of age are very rarely affected. However, in HIV-infected individuals, reactivation of the Epstein-Barr virus can occur at any age.

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