Synergistic Inhibition of Epstein-Barr Virus: Transformation of B Lymphocytes by and Interferon and by 3'-Azido-3'-Deoxythymidine

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Abstract
We analyzed the effects of 3′-azido-3′-deoxythymidine (AZT) and α and γ interferon (1FN-α and IFN-γ) on transformation of human umbilical cord lymphocytes (HUCLs) by Epstein-Barr virus (EBV). B lymphocytic outgrowth from HUCLs infected with EBV was monitored by focus formation; the presence of EBV genomes in transformed foci was confirmed by in situ cytohybridization and EBV nuclear antigen. The 50% inhibitory doses for preventing focus formation were 0.14 µM for AZT, 10 units (U)/mL for IFN-α, and 1 U/mL for IFN-γ. To determine whether inhibition resulted from direct cytotoxic effects, we assessed the viability of non transformed HUCLs exposed to the agents for 30 d. The nontoxic doses were 1 µM for AZT, 30 U/mL for IFN-α, and 3 U/mL for IFN-γ. Combining IFN-α or IFN-γ with AZT or IFN-α with IFN-γ at nontoxic doses showed synergistic decreases in numbers of transformed foci. Transformation of HUCLs by EBV was sensitive to, but not abolished by, these agents at doses below those required for cell killing.

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