HOST IMMUNITY TO EBV INFECTION IN VITRO AND IN VIVO

eb病毒（EBV）是一种携带的持续性疱疹病毒

Epstein-Barr virus (EBV) is a persistent herpesvirus that is carried latently and reactivates, usually without harm to the infected individual. EBV infects and "immortalizes" or "growth transforms" normal resting human B cells in vitro driving them to become latently infected proliferating lymphoblasts. The virus also plays a central role in several human diseases, including several B cell neoplasias. The goal of this proposal will be to investigate the relationship between normal B cell biology and the establishment of a latent, persistent infection by Epstein-Barr virus. Specifically, we will address two aspects of this relationship. First, we will undertake a detailed analysis of how a model B cell activation gene (Blast-1) is regulated. Blast-1 is an adhesion molecule, restricted in its expression to lymphoid and myeloid cells, that is upregulated by EBV infection. We will map the minimal promoter and the sequences responsible for tissue specific expression. We will establish the relative roles of increased transcription and mRNA stabilization in activation by EBV. Regulatory elements so defined will be mapped. The mechanism will then be compared to that of other known activators including IL-4, PMA, IL-lb and ionomycin. Second, we will study the relationship between the form of the persistent viral genome and the differentiation stage of the infected cell. Specifically, we will investigate the role of cellular activation stage in determining whether the virus persists as an episome or integrated. The viral sequences involved in episomal amplification will be investigated. Previously identified integration sites will be cloned and sequenced to investigate the mechanism of integration. Lastly, tumor cell lines will be tested for the presence of integrated EBV genomes by the fluorescence in situ hybridization technique to provide a definitive answer as to whether such sequences are or are not present.