| Disease: | Comments: |
| Infectious mononucleosis ("glandular fever") | Primary infection, self limiting. Occurs in ~50% of primary infections of adolescents and young adults. |
| Burkitt's lymphoma | EBV found as latent infection in 97% of endemic, 15–85% of sporadic and 30–40% of AIDS-linked Burkitt's lymphoma cases. |
| Hodgkin's disease | Sporadic lymphoma; latent EBV found in ~50% of cases. |
| B-lymphoproliferative disease | Lymphoproliferative disease/lymphomas, almost exclusively in the immunocompromised host, especially post-transplant (as a result of immunosuppressive drug therapy) and in AIDS. Might occur in primary infection or persistent infection. |
| X-linked lymphoproliferative syndrome | Rare genetic immune dysfunction results in fatal primary infection (see below). |
| Nasopharyngeal carcinoma | Malignant squamous epithelial tumour of the nasopharynx; cells contain latent virus. |
| Oral hairy leukoplakia | Viral replication in the superficial layers of tongue epithelium results in a benign lesion, almost exclusively in HIV-positive individuals. |
There is a well-established relationship between EBV and oncogenesis - Burkitts lymphoma and nasopharyngeal carcinoma. Infection is also associated with B cell lymphomas in immunosuppressed patients, certain T cell lymphomas, and Hodgkin's disease. The complete nucleotide sequence (~172kbp) is known, and contains many internal repeats.
EBV is a powerful transforming agent for normal resting human B lymphocytes in vitro, resulting in the outgrowth of EBV-immortalized lymphoblastoid cell lines (LCL). EBV gene expression in LCL is restricted to about nine of the approximately 100 genes encoded by the virus, and since LCL are largely non-permissive for virus production, the EBV genes expressed in LCL are defined as latent genes. Six of the latent genes encode the nuclear antigens:
EBNA-1, EBNA-2, EBNA-3A, EBNA-3C and LMP-1 are essential for EBV-induced transformation of B cells, while EBNA-LP and LMP-2A enhance the transformation efficiency. The process of cellular transformation by EBV is not completely understood. In EBV-associated malignancies, not all of the transforming proteins are expressed: in Burkitt's lymphoma, only EBNA-1 is regularly detected, while in nasopharyngeal carcinoma, EBNA-1 is the only protein invariably expressed but many tumours also express LMP-1 and LMP-2. A number of reasons may be put forward to explain these observations:
X-linked lymphoproliferative syndrome (XLP) is a rare condition usually seen in males where on initial infection with EBV (usually around the age of 2-3) results in a hyperimmune response, sometimes causing a fatal form of glandular fever and sometimes cancer of the lymph nodes. Death by the age of 40 is inevitable. XLP is an inherited defect due to a faulty gene on the X chromosome. Females have two X chromosomes, so if one copy is faulty, the other can usually compensate. But males have just one X chromosome and one Y. There is no backup X, hence the predominance of the disease in males. The gene responsible (SH2D1A or SAP) causes a failure in the communication between the cells of the immune system. A protein known as SLAM ("signalling lymphocyte activation molecule") stimulates activity and proliferation of cells in the immune system. SLAM is found on the surface of both B and T cells, effectively coupling them together. When this happens, it signals changes inside the cells that cause them to become active and to develop and proliferate. SAP ("SLAM-associated protein") is produced by T cells, and is an inhibitor of SLAM. This is the gene which is defective in XLP. EBV first infects the throat but shortly afterwards invades the B cells, and triggers them to multiply, partly by increasing the number of SLAM proteins on the surface. Without functional SAP protein, the body is unable to control the B-cell proliferation triggered by infection. T cells recognize the EBV-infected B cells as foreign and instigate a massive inflammatory response (J.Sayos et al. Nature 395: 462-469, 1998).
Therapy/Vaccine - none.