GROWTH ARREST OF EPSTEIN-BARR-VIRUS IMMORTALIZED B-LYMPHOCYTES BY ADENOVIRUS-DELIVERED RIBOZYMES

Epstein-Barr virus (EBV) infection is associated with several human di seases that involve unrestricted proliferation of B lymphocytes, EBV n uclear antigen 1 (EBNA-1) is expressed in all EBV-infected cells and p lays an essential role in persistence of the EBV genome. EBNA-1 has al so been reported to have oncogenic potential, As an approach for treat ing EBV infections, we examined the capacity of EBNA-1 ribozymes deliv ered by recombinant adenoviruses to suppress EBNA-1 expression and to block virus-induced B cell proliferation, In contrast to primary B cel ls, EBV-transformed B lymphoblastoid cell lines expressed cry integrin s, the adenovirus internalization receptors, and were also susceptible to adenovirus-mediated gene delivery, Adenovirus delivery of a specif ic ribozyme (RZ1) to lymphoblastoid cell lines, suppressed EBNA-1 mRNA and protein expression, significantly reduced the number of EBV genom es, and nearly abolished cell proliferation in low serum, Adenovirus d elivery of RZ1 also prevented EBV infection of an established EBV-nega tive B cell line, These studies demonstrate the potential use of adeno virus-encoded ribozymes to treat EBV-induced lymphoproliferative disor ders.