The long term objective of this study is to develop a deeper understanding of persistent infection with Epstein-Barr virus (EBV). EBV has the capacity to drive the proliferation of resting B lymphocytes and this makes it a risk factor for human cancers such as Hodgkin's disease, Burkitt's lymphoma, immunoblastic lymphoma and nasopharyngeal carcinoma. However, the virus is able to persist in a quiescent state in vivo where it specifically targets resting memory B cells. By understanding how EBV can persist in most individuals without causing disease we hope to gain insight into what goes wrong when the virus does cause neoplastic disease. This study wilt employ sophisticated cell fractionation techniques and quantitative RealTime DNA and RT PCR assays to address four unresolved issues around EBV persistence. 1. Does acute EBV infection, infectious mononucleosis (AIM), represent a disordered state of EBV infection or simply an amplified version of the stable, long term carrier state? 2. Does EBV, like other herpesviruses, shut off the expression of all protein coding genes when it reaches its final site of persistence - long lived memory B cells in the peripheral blood? 3. What is the nature and origin of the latently infected memory cells proposed as the site of EBV persistence? Are they bona fide memory cells? Does antigen play a role in the production and/or maintenance of these memory cells or do latent proteins perform these functions? How rapidly do the infected cells turn over? 4. Are epithelial cells of the nasopharyngeal lymphoid system e.g. tonsils infected with EBV in vivo or infectable in vitro? Previous studies have analyzed EBV infection of epithelial cell lines and tissues from sites other than the site of persistent infection - the nasopharyngeal lymphoid tissue. However, epithelial tissues are biologically diverse so we will focus our studies on the biologically relevant epithelium from the tonsil.
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