Background Information

Epstein-Barr Virus (EBV)

Epstein-Barr virus (EBV) is a gamma-1 herpes virus, discovered by Tony Epstein, Yvonne Barr and Burt Achong in 1964 and is found throughout all human populations with a prevalence of 90% in adults. Primary EBV infections usually occurs asymptomatic in childhood and latently persists during life-time; it is spread by saliva and initially infects the epithelial cells of the oropharynx where it replicates and infects B-cells, resulting in EBV driven B cell proliferation which may result in infectious mononucleosis; particularly in young adults. Migrating, latent infected B-cells are thought to be the source of continued virus spreading. Normally, the infection is brought under control by cytoxic T-cells. In males with X-linked proliferative disorders however, it may result in fatal infectious mononucleosis. The EBV virus is directly associated with human cancers such as Burkitt's lymphoma, Post transplant lymphoproliferative disease-like lymphomas in immune-comprised individuals (transplant patients and persons infected with AIDS), Hodgkin disease and nasopharyngeal carcinoma which is a common carcinoma in South East Asia. EBV infection is also a significant problem in AIDS patients where it is associated with diffuse polyclonal lymphomas, lymphocytic interstitial pneumonia and oral hairy leucoplakia of the tongue.

Like other herpes viruses, EBV infects non dividing cells which are in case of EBV, mature resting B-cells. The virus triggers the cells to start proliferation (going from G0 to G1) by linking to the CD21 molecule and sustains the proliferation by the autocrine production of B cell growth cytokines. In the lytic cycle early and late genes are expressed resulting in a productive infection. In the latency cycle immediate early genes are not expressed but a large amount of genetic information is devoted to the latent state of mitotic B-cells. At least 11 EBV genes are expressed during latent infection. Two of those are small non-coding RNAs (EBER 1 and EBER 2), six encode nuclear proteins (EBNAs and LP) and three encode membrane proteins (LMPs). Together these proteins lead to cellular immortalization which involves both increased cellular survival and proliferation. The EBER genes are transcribed by RNA polymerase and are the most abundant EBV transcripts in Burkitt lymphoma and other latent infected cells. EBERS induce transcription of interleukin10 which acts as an autocrine growth factor of Burkitt lymphoma. In Burkitt lymphoma, the EBV virus up-regulates BCL-2 in concert with a down regulation of c-Myc causing inhibition of apoptosis, thus promoting tumor genesis.

PanPath's REMBRANDT® kit for EBV is designed for active EBV infection. This kit contains a labeled probe that targets the W fragment (3.0 Kb) and shows no cross-hybridization with other viral DNA targets, provided that the hybridization conditions as laid out in the protocol are strictly followed.

PanPath's REMBRANDT® kit for EBER is designed for the detection of latent EBV infections; however, usage of PanPath's EBER probe will also yield hybridization signals in tissue sections with lytic EBV infections. The labeled oligonucleotide probe for EBER provided in this kit is a mixture of 5 oligonucleotides complementary to EBER type 1 and EBER type 2 RNAs.