ERADICATION OF LATENT EPSTEIN-BARR-VIRUS BY HYDROXYUREA ALTERS THE GROWTH-TRANSFORMED CELL PHENOTYPE

The hallmark of infection by human herpesviruses, life-long persistenc e in the host, is unaffected by current antiviral therapies effective against replication of virus. In vitro studies indicated that low conc entrations of the ribonucleotide reductase inhibitor, hydroxyurea, com pletely eliminated Epstein-Barr virus (EBV) episomes from latently inf ected Burkitt's lymphoma (BL) cell subsets, providing the first exampl e of chemotherapeutic eradication of a latent herpesvirus from any cel l population. Unlike parental EBV-positive BL cells. virus-free cell p rogeny from one treated cell line no longer exhibited the malignant ph enotype in tumorigenicity assays. Hydroxyurea-treated primary B lympho cytes immortalized by EBV ceased to proliferate as episomes were lost. The altered growth phenotype of both BL cells and immortalized primar y B cells suggests that latent EBV is an appropriate and accessible th erapeutic target for treatment of some EBV-induced lymphoproliferation s.