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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Cohen, Jeffrey I (2018) Author Correction: New activities for old antibiotics. Nat Microbiol 3:844
Cohen, Jeffrey I (2018) New activities for old antibiotics. Nat Microbiol 3:531-532
Bollard, Catherine M; Cohen, Jeffrey I (2018) How I treat T-cell chronic active Epstein-Barr virus disease. Blood 131:2899-2905
Sadaoka, Tomohiko; Schwartz, Cindi L; Rajbhandari, Labchan et al. (2018) Human Embryonic Stem Cell-Derived Neurons Are Highly Permissive for Varicella-Zoster Virus Lytic Infection. J Virol 92:
Cohen, Jeffrey I (2018) Herpesviruses in the Activated Phosphatidylinositol-3-Kinase-? Syndrome. Front Immunol 9:237
Coghill, Anna E; Bu, Wei; Hsu, Wan-Lun et al. (2018) Evaluation of Total and IgA-Specific Antibody Targeting Epstein-Barr Virus Glycoprotein 350 and Nasopharyngeal Carcinoma Risk. J Infect Dis 218:886-891
Burbelo, Peter D; Gunti, Sreenivasulu; Keller, Jason M et al. (2017) Ultrarapid Measurement of Diagnostic Antibodies by Magnetic Capture of Immune Complexes. Sci Rep 7:3818
Cohen, Jeffrey I (2017) GATA2 Deficiency and Epstein-Barr Virus Disease. Front Immunol 8:1869
Wang, Kening; Hoshino, Yo; Dowdell, Kennichi et al. (2017) Glutamine supplementation suppresses herpes simplex virus reactivation. J Clin Invest 127:2626-2630
Liu, XueQiao; Cohen, Jeffrey I (2016) Epstein-Barr Virus (EBV) Tegument Protein BGLF2 Promotes EBV Reactivation through Activation of the p38 Mitogen-Activated Protein Kinase. J Virol 90:1129-38

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