MODEL OF EPSTEIN-BARR-VIRUS INFECTION OF HUMAN THYMOCYTES - EXPRESSION OF VIRAL GENOME AND IMPACT ON CELLULAR RECEPTOR EXPRESSION IN THE LYMPHOBLASTIC CELL-LINE, HPB-ALL

Infection of B lymphocytes and epithelial tissue by Epstein-Barr virus (EBV) is associated with malignancy and autoimmunity. The cellular re ceptor for EBV has been identified as CD21 (CR2). A molecule, which is biochemically and immunologically similar to B-cell CD21, has been id entified on a subpopulation of immature thymocytes, suggesting a role for this molecule in the regulation of T-cell development and further suggesting that immature T cells might be susceptible to EBV infection . A growing body of literature now documents the presence of EBV in tu mors of T-cell origin. We have evaluated the susceptibility of the hum an immature T cell line, HPB-ALL, to infection by EBV. Electron micros copy studies showed a rapid internalization of virus by HPB cells. Sou thern blotting showed the intracellular presence of linear EBV genomes , and components of the virus replicative cycle were identified. Expre ssion of the BamHI Z region of the genome, encoding the nuclear protei n, ZEBRA, which is strictly associated with productive infection in B cells, was detected in HPB-ALL cells. A spliced variant of Z, RAZ, was also identified. Cell surface expression of EBV late antigens was obs erved to occur transiently. Infection of HPB cells was also accompanie d by altered expression of T-cell surface molecules involved in antige n recognition, a process critical to normal development of the T-cell repertoire. Delineation of the outcome of T-cell infection by EBV may lead to a better understanding of the role of this virus in autoimmune processes and malignancy. (C) 1995 by The American Society of Hematol ogy.