Epstein Barr Virus Associated Lymphoproliferative Disorders in Immunocompromised Individuals

EBV is a gamma herpes virus, a subfamily distinguished by its limited tissue tro-pism and latency. EBV enters via the oropharyngeal route and infects resting B lymphocytes through the interaction between the EBV viral envelope glycoprotein (gp350/220) and the C3d complement receptor (CD21). Infected B cells induce the immunologic response of both virus-specific and virus-nonspecific T cells during primary infection, which leads to regression of a majority of infected B cells. However, the virus persists in its latent state lifelong, by its continued presence in a small number of B cells, which express latent membrane protein 2A (LMP 2A) and small EBV encoded RNA 1 and 2 (EBERs 1 and 2). See the following listing of the functions of EBV latent antigens.

Functions of EBV Latent Antigens

EBV antigen Function

LMP 1 Prevents apoptosis (through NF-kB and MAPK, induction of antiapoptotic proteins AP-1, bcl-2) and immortalization of B cells, increase in tumor invasiveness (by induction of matrix metalloproteinase). LMP 2A Inhibits lysis of B cells.

Lytic antigens vIL-10 and BHRF1 facilitate lysis of cells and induce survival and proliferation of nearby latently infected B cells. EBNA 1 Maintains and replicates the EBV episome in latency.

EBNA 2 Has an immortalizing function.

Abbreviations: MAPK, mitogen-activated protein kinase; NF-kB, nuclear factor kB; vIL-10, viral homolog of cellular interleukin-10; BHRF1, viral homolog of cellular bcl-2; bcl-2, B cell lymphoma protein.

EBV Antigens Associated with the Lytic Cycle

Early antigen (EA) Viral capsid antigen (VCA).

During acute infectious mononucleosis (AIM), humoral responses are directed against both lytic and latent proteins. IgM antibodies to cellular proteins and heterophile antigens are also present during AIM.

Detectable levels of IgG antibodies to VCA and EBNA 1 persist through lifetime. In conjunction with humoral response, the CD4 and CD8 T cell-mediated responses also play an important role in controlling the EBV infection by identifying and destroying latently infected cells.

Cellular Responses in the Control of EBV Infection

The lymphocytosis during AIM consists of activated CD4 and CD8 T lymphocytes. They are specific for EBV lytic and latent proteins.

Cell

Reactivity (function)

CD8+, CD4+ T cells

Directed toward latent phase proteins: EBNA 3, EBNA 4,

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