Yonsei Med J.  2006 Apr;47(2):287-290. 10.3349/ymj.2006.47.2.287.

Evidence that Amphotericin B Mediates Reactivation of Latent Epstein-Barr Virus in Hodgkin's Lymphoma Allowing Cytotoxicity by Acyclovir

• Kast RE

• KMID: 1110758
• DOI: http://doi.org/10.3349/ymj.2006.47.2.287

Abstract

This brief communication focuses on aspects of a recent case report (Yonsei Med J 2005;46:425-30) on a full and sustained remission of Hodgkin's lymphoma (HL) after a single day of chemotherapy. A septic episode required stopping chemotherapy and starting amphotericin B and acyclovir. Remission evidence was seen within days of starting these. A review of research supporting the notion that amphotericin B can reactivate latent Epstein-Barr virus and thus allow acyclovir to kill infected HL cells is given. Experimental work is required to confirm or refute this possibility. If successful, amphotericin B and acyclovir treatment could be extended to other EBV-driven cancers such as Burkitt's lymphoma, nasopharyngeal carcinoma and the occasional EBV-related epithelial cancer of the breast, colon, prostate, and others.

Keyword

Acyclovir; amphotericin B; Coley's toxin; Epstein-Barr virus; ganciclovir; Hodgkin's lymphoma; remission; TNF-alpha

MeSH Terms

Virus Activation
Tumor Necrosis Factor-alpha/metabolism
Remission Induction
Humans
Hodgkin Disease/*drug therapy/pathology/*virology
Herpesvirus 4, Human/*metabolism
Ganciclovir/therapeutic use
*Drug Synergism
Burkitt Lymphoma/virology
Anti-Bacterial Agents/pharmacology
Amphotericin B/*pharmacology
Acyclovir/*therapeutic use

Reference

1. Bang SM, Cheong JW, Yang WI, Hahn JS. An unusual case of spontaneous remission of Hodgkin's disease after a single cycle of COPP-ABV chemotherapy followed by infectious complications. Yonsei Med J. 2005. 46:425–430.

2. Wiemann B, Starnes CO. Coley's toxins, tumor necrosis factor and cancer research: a historical perspective. Pharmacol Ther. 1994. 64:529–564.

3. Kuppers R, Hansmann ML. The Hodgkin and Reed Sternberg cell. Int J Biochem Cell Biol. 2005. 37:511–517.

4. Marshall NA, Christie LE, Munro LR, Culligan DJ, Johnston PW, Barker RN, et al. Immunosuppressive regulatory T cells are abundant in the reactive lymphocytes of Hodgkin's lymphoma. Blood. 2004. 103:1755–1762.

5. Crumpacker CS. Ganciclovir. N Engl J Med. 1996. 335:721–729.

6. Faller DV, Mentzer SJ, Perrine SP. Induction of the Epstein-Barr virus thymidine kinase gene with concomitant nucleoside antivirals as a therapeutic strategy for Epstein-Barr virus-associated malignancies. Curr Opin Oncol. 2001. 13:360–367.

7. Feng WH, Hong G, Delecluse HJ, Kenney SC. Lytic induction therapy for Epstein-Barr virus-positive B-cell lymphomas. J Virol. 2004. 78:1893–1902.

8. Feng WH, Cohen JI, Fischer S, Li L, Sneller M, Goldbach-Mansky R, et al. Reactivation of latent Epstein-Barr virus by methotrexate: a potential contributor to methotrexate-associated lymphomas. J Natl Cancer Inst. 2004. 96:1691–1702.

9. Daibata M, Bandobashi K, Kuroda M, Imai S, Miyoshi I, Taguchi H. Induction of lytic Epstein-Barr virus (EBV) infection by synergistic action of rituximab and dexamethasone renders EBV-positive lymphoma cells more susceptible to ganciclovir cytotoxicity in vitro and in vivo. J Virol. 2005. 79:5875–5879.

10. Israel BF, Kenney SC. Virally targeted therapies for EBV-associated malignancies. Oncogene. 2003. 22:5122–5130.

11. Neyts J, Sadler R, De Clercq E, Raab-Traub N, Pagano JS. The antiviral agent cidofovir[(S)-1-(3-hydroxy-2-phosphonyl-methoxypropyl)cytosine] has pronounced activity against nasopharyngeal carcinoma grown in nude mice. Cancer Res. 1998. 58:384–388.

12. Razonable RR, Henault M, Lee LN, Laethem C, Johnston PA, Watson HL, et al. Secretion of proinflammatory cytokines and chemokines during amphotericin B exposure is mediated by coactivation of toll-like receptors 1 and 2. Antimicrob Agents Chemother. 2005. 49:1617–1621.

13. Sau K, Mambula SS, Latz E, Henneke P, Golenbock DT, Levitz SM. The antifungal drug amphotericin B promotes inflammatory cytokine release by Toll-like receptor- and CD14-dependent mechanism. J Biol Chem. 2003. 278:37561–37568.

14. Murakawa M, Shibuya T, Teshima T, Kudo J, Okamura T, Harada M, et al. Spontaneous remission from acute exacerbation of chronic adult T-cell leukemia. Blut. 1990. 61:346–349.

15. Malewicz B, Momsen M, Jenkin HM, Borowski E. Potentiation of antiviral activity of acyclovir by polyene macrolide antibiotics. Antimicrob Agents Chemother. 1984. 25:772–774.