We have been searching for new therapies for treatment of virus infections. Last year we concluded a clinical study using CMX-001, a lipid-conjugated form of cidofovir, which has excellent oral bioavailability and lacks the kidney toxicity of cidofovir, in patients with severe herpes simplex, cytomegalovirus, and adenovirus infections. We have also been searching for new viruses in persons with unexplained diseases. Last year we studied cohorts of patients with chronic fatigue syndrome and chronic inflammatory diseases of unknown etiology and did not detect evidence of XMRV infection in these patients. We have also been testing other compounds in vitro for their activity against herpesviruses. Ascorbic acid (vitamin C) has previously been shown to kill various cancer cell lines in vitro at levels that can be achieved in the serum of humans with intravenous dosing. This year we found that Epstein-Barr virus (EBV)-positive Burkitt lymphoma cells were more susceptible to killing by ascorbic acid than EBV-negative Burkitt lymphoma cells or EBV-transformed B cells. Ascorbic acid did not induce programmed cell death (apoptosis) in any of the cells tested, but did induce the production of reactive oxygen species and cell death. Previously, we showed that bortezomib, a proteasome inhibitor that is approved for the treatment of multiple myeloma, induces death of EBV-transformed B cells and EBV-positive Burkitt lymphoma cells. We found that ascorbic acid is strongly antagonistic for bortezomib-induced cell death in EBV-transformed B cells and EBV-positive Burkitt lymphoma cells. Finally, ascorbic acid did not prolong survival of severe combined immunodeficiency mice inoculated with EBV-transformed B cells either intraperitoneally or subcutaneously. Thus, while ascorbic acid was highly effective at killing EBV-positive Burkitt lymphoma cells and EBV-transformed B cells in vitro, it antagonized cell killing by bortezomib and was ineffective in an animal model.

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