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


CONCLUSIONS
The present results indicate that vidarabine and/or foscarnet may be effective for preventive treatment of EBV-associated NK-GLPD.
Ishii
Masaru
M
Department of Internal Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871.
Yamaguchi
Norihiko
N
Ohshima
Shiro
S
Ishii
Taeko
T
Mori
Kiyoshi L
KL
Kimura
Hiroshi
H
Morishima
Tsuneo
T
Kawase
Ichiro
I
Saeki
Yukihiko
Y
D000293:Adolescent; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002455:Cell Division / Q000187:drug effects; D002908:Chronic Disease; D009033:Culicidae; D020031:Epstein-Barr Virus Infections / Q000150:complications*; D005260:Female; D017245:Foscarnet / Q000627:therapeutic use; D006801:Humans; D007299:Insect Bites and Stings / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D008232:Lymphoproliferative Disorders / Q000517:prevention & control* / Q000821:virology*; D014740:Vidarabine / Q000627:therapeutic use; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D017245:Foscarnet; D014740:Vidarabine