Possibility of preventive treatment for EBV-associated NK cell-lineage proliferative disorders

Abstract

Objective. Chronic active EBV infections (CAEBV) are often causative of malignant lymphoproliferative disorders, such as natural killer (NK) cell-lineage granular lymphocyte proliferative disorders (NK-GLPD), which are refractory to several conventional chemotherapies and usually show a poor prognosis. To explore the possibility of preventive treatment for Epstein-Barr virus (EBV)-infected NK-GLPD, we examined the effect of antiviral drugs on EBV-infected pre-malignant NK cells. Methods. EBV-infected pre-malignant NK cells (P-NK cells) were isolated from the periphery of a patient suffering from severe hypersensitivity to mosquito bites (SHMB). Abnormal oligoclonal expansion of EBV-infected CD56(+)/CD3(-) NK cells was observed in her periphery. Effects of several antiviral drugs were examined both on the proliferation and on EBV-replication of P-NK cells. Results. Vidarabine and foscarnet, but not acyclovir nor gancyclovir, significantly suppressed both the proliferation and EBV-DNA replication of P-NK cells in a dose-dependent manner, whereas these drugs did not suppress the proliferation of YT, which is an EBV-infected malignant NK cell line. The combination of vidarabine and foscarnet had an additive effect and almost completely suppressed the proliferation of P-NK cells. Conclusion. The present results indicate that vidarabine and/or foscarnet may be effective for preventive treatment of EBV-associated NK-GLPD.