Epstein-Barr Virus

Structure and Antigenic Composition

EBV virions were first discovered using electron microscopy in biopsy samples of Burkitt lymphoma. The pathogenicity of the virus and its ability to evade the immune response are determined by a complex set of antigens and molecules:

• VCA (Viral Capsid Antigen): a viral capsid antigen that plays a key role in the early stages of infection.
• EBNAs (Epstein–Barr Nuclear Antigens): a group of nuclear antigens (types 1, 2, 3A, 3B, 3C). By nature, these are DNA-binding proteins. The EBNA-1 protein is critical for the development of the infection itself, while EBNA-2 is responsible for the immortalization (infinite division) of infected cells.
• LMPs (Latent Membrane Proteins): latent membrane proteins of the first and second types. These exhibit pronounced oncogene-like activity by interfering with the cell cycle.
• EBER (Epstein–Barr Encoded RNAs): small viral RNAs (EBER1 and EBER2) involved in the regulation of viral activity.

Epidemiology and pathogenesis

The infection has low contagiousness; the source of infection is a sick person or an asymptomatic virus carrier. Transmission occurs primarily via airborne droplets or contact (through saliva). There is a high level of herd immunity in the population—specific antibodies are detected in the vast majority of people.

The entry portal is the mucosa of the oropharynx. The virus finds its main target—B lymphocytes—by binding to their surface CD21 receptor. Upon entering, EBV does not simply destroy the cell, but acts as a mitogen, stimulating active multiplication (proliferation) of B lymphocytes.

The infection is prone to latency. The virus persists for life in B cells and forms latent foci in lymphoid tissue (primarily in the palatine tonsils), as well as in the epithelial cells of the oropharynx and salivary glands. Even after clinical recovery (at the convalescence stage), the virus continues to be actively shed from the nasopharyngeal and oral mucosa for several months.

Clinical Forms: Mononucleosis and Chronic Infection

Epstein-Barr virus can cause asymptomatic carriage, as well as acute and chronic forms of the disease.

Acute Form (Infectious Mononucleosis) The classic manifestation of primary contact with the virus. The disease is accompanied by severe malaise and high fever. Mononucleosis is characterized by the classic clinical triad:

1. Oropharyngeal involvement (pronounced tonsillitis with involvement of the palatine and pharyngeal tonsils).
2. Lymphadenopathy (generalized enlargement of lymph nodes).
3. Hepatosplenomegaly (enlargement of the liver and spleen).

Pronounced intoxication and specific shifts in the hemogram are also observed.

Chronic Infection May present as a cyclical recurrent disease. Main symptoms are blurred: persistent low-grade fever, sore throat, headaches, and pathological fatigue.

In AIDS patients, a specific lesion of the oral mucosa occurs—hairy oral leukoplakia—which is considered an important marker condition.

Oncogenesis and Lymphoproliferative Diseases

Since EBV is a potent mitogen for B lymphocytes, it has direct oncogenic potential. The risk of developing tumors directly depends on the competence of the T-cell arm of the immunity.

In risk groups (patients with T-cell immune defects, HIV infection, genetic X-linked lymphoproliferative disease, as well as individuals receiving immunosuppressive therapy in transplantology), severe pathologies may develop instead of classic mononucleosis: a polyclonal leukemia-like B-cell disease or various lymphomas.

Specific tumors associated with the virus:

• Burkitt Lymphoma: an African endemic form, the development of which is closely linked to malaria.
• Hodgkin Lymphoma: in a significant proportion of cases, tumor cells contain viral DNA.
• Nasopharyngeal Carcinoma: endemic to Eastern countries. Unlike lymphomas, this pathology affects epithelial rather than lymphoid cells, in which viral DNA is also detected.

Immunity and Laboratory Diagnostics

Specific antiviral drugs and vaccines against EBV have not yet been developed. The developing immunity is persistent—cases of recurrent disease have not been described. Cytotoxic CD8+ lymphocytes play the main role in the cellular response, while the production of specific antibodies plays the main role in the humoral response.

Diagnostics is based on several methods:

1. Hematological Analysis: pronounced lymphocytosis is characteristic, with the proportion of monocytes reaching 60–70% of all leukocytes. A key marker of mononucleosis is the appearance of atypical lymphocytes (mononuclear cells) in the blood at about 30%.
2. Serology (ELISA):
3. Acute (Recent) Infection: IgM class immunoglobulins to the capsid antigen (VCA) are detected, and a rise in antibody titer to the nuclear antigen (EBNA) is observed.
4. Height or Past Infection: IgGs to the VCA antigen appear.
5. Auxiliary Methods: detection of heterophile antibodies using the sheep erythrocyte agglutination reaction.

Briefly: answers to topical questions

Class and exam questions

What else to study on this topic

• The mechanism of B-lymphocyte immortalization by the nuclear antigen EBNA-2.
• Oncogene-like action of latent membrane proteins (LMP-1 and LMP-2).
• Features of the development of post-transplant lymphoproliferative disorder under immunosuppression.
• The pathogenetic link between endemic malaria and the development of the African form of Burkitt lymphoma.
• Detailed interpretation of the serological profile (ELISA) at various stages of infection.

Other topics in the section "DNA viruses (parvoviruses, papillomaviruses, adenoviruses, hepatitis B, herpes viruses, poxviruses, anelloviruses)"

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