Biochemical and genetic studies of Epstein-Barr virus latent membrane protein 2

Abstract

Epstein-Barr Virus (EBV) causes infectious mononucleosis in normal adolescents and malignant B lymphocyte proliferation in immune compromised patients, in marmosets, or upon transfer of infected human B lymphocytes into SCID mice. EBV is also etiologically associated with African Burkitt's lymphoma, Hodgkin's Disease, and nasopharyngeal cancer. EBV transformed, latently infected B lymphocytes contain EBV episomes and eight virus encoded proteins. Six are nuclear proteins (EBNAs) and two are the integral membrane proteins, LMP1 and LMP2. These eight proteins are presumed to mediate latent virus infection or B lymphocyte proliferation and are thus under intense scrutiny. Besides EBNA1, which is required for episome maintenance, LMP1 and LMP2, are the two transformation associated proteins that are most consistently detected in EBV related malignancies, and the LMP2 message is the only message detected in PCR analysis of B lymphocytes from individuals harboring EBV latent infections. LMP2 associates with src family tyrosine kinases, a 70 kda cell phosphoprotein, LMP1 and several other unidentified cell proteins. LMP1 is a key mediator of EBV's effects on inducing B lymphocyte activation and adhesion molecules and is a transforming oncogene in rodent fibroblasts. The association of these two EBV encoded membrane proteins could create a macromolecular complex mediating constitutive B lymphocyte activation through normal cell signal transduction pathways. LMP2 might may control activation of lytic replication or down regulate the activation state of EBV infected cells allowing persistence in the human host.