Chapter 181

### Definition

Epstein-Barr virus (EBV) is the cause of heterophile-positive infectious mononucleosis (IM), which is characterized by fever, sore throat, lymphadenopathy, and atypical lymphocytosis. EBV is also associated with several human tumors, including nasopharyngeal carcinoma, Burkitt's lymphoma, Hodgkin's disease, and (in patients with immunodeficiencies) B cell lymphoma. The virus is a member of the family Herpesviridae. The two types of EBV that are widely prevalent in nature are not distinguishable by conventional serologic tests.

### Epidemiology

EBV infections occur worldwide. These infections are most common in early childhood, with a second peak during late adolescence. By adulthood, more than 90% of individuals have been infected and have antibodies to the virus. IM is usually a disease of young adults. In lower socioeconomic groups and in areas of the world with deficient standards of hygiene (e.g., developing regions), EBV tends to infect children at an early age, and IM is uncommon. In areas with higher standards of hygiene, infection with EBV is often delayed until adulthood, and IM is more prevalent.

EBV is spread by contact with oral secretions. The virus is frequently transmitted from asymptomatic adults to infants and among young adults by transfer of saliva during kissing. Transmission by less intimate contact is rare. EBV has been transmitted by blood transfusion and by bone marrow transplantation. More than 90% of asymptomatic seropositive individuals shed the virus in oropharyngeal secretions. Shedding is increased in immunocompromised patients and those with IM.

### Pathogenesis

EBV is transmitted by salivary secretions. The virus infects the epithelium of the oropharynx and the salivary glands and is shed from these cells. While B cells may become infected after contact with epithelial cells, studies suggest that lymphocytes in the tonsillar crypts can be infected directly. The virus then spreads through the bloodstream. The proliferation and expansion of EBV-infected B cells along with reactive T cells during IM result in enlargement of lymphoid tissue. Polyclonal activation of B cells leads to the production of antibodies to host-cell and viral proteins. During the acute phase of IM, up to 1 in every 100 B cells in the peripheral blood is infected by EBV; after recovery, 1–50 in every 1 million B cells is infected. During IM, there is an inverted CD4+/CD8+ T cell ratio. The percentage of CD4+ T cells decreases, while there are large clonal expansions of CD8+ T cells; up to 40% of CD8+ T cells are directed against EBV antigens during acute infection. Memory B cells, not epithelial cells, are the reservoir for EBV in the body. When patients are treated with acyclovir, shedding of EBV from the oropharynx stops but the virus persists in B cells.

The EBV receptor (CD21) on the surface of B cells is also the receptor for the C3d component of complement. EBV infection of epithelial cells results in viral replication and production of virions. ...

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