Leukoregulin, a novel cytokine enhances the anti-herpesvirus actions of acyclovir.
Leukoregulin is a naturally occurring immunologic cytokine which increases membrane permeability and drug uptake in tumor cells but not in normal cells. In this paper we show that leukoregulin also increases membrane permeability of Herpes simplex virus type 1 (HSV-1)-infected cells. More importantly, we demonstrate that leukoregulin significantly enhances the ability of acyclovir (acycloguanosine, ACV) to inhibit the cellular release of infectious HSV-1. The ability of 1-100 microM ACV to inhibit infectious HSV-1 production is increased up to 100-fold when HSV-1-infected human amnion (WISH) cells are treated with 5 units leukoregulin/ml and ACV 3 hr after virus infection. Under these conditions, leukoregulin alone is unable to inhibit HSV-1 infectivity. In addition, three unrelated cytokines, interleukin-1 alpha (IL-1), interferon (IFN)-alpha and IFN-gamma lack the ability to enhance the anti-HSV actions of ACV when their treatment is initiated after HSV-1 infection. These findings demonstrate that a combination of immunotherapy and chemotherapy can produce a substantial inhibition of herpesvirus replication and provide a rationale for the application of this approach to the interventive treatment of virus infection.
Hooks
J J
JJ
Immunology & Virology Section, National Eye Institute, Bethesda, Maryland 20892.
Detrick
B
B
Evans
C H
CH
D000212:Acyclovir / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002463:Cell Membrane Permeability / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005434:Flow Cytometry; D007370:Interferon Type I / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D008222:Lymphokines / Q000494:pharmacology*; D018139:Simplexvirus / Q000187:drug effects* / Q000472:pathogenicity / Q000502:physiology; D014779:Virus Replication / Q000187:drug effects
D000970:Antineoplastic Agents; D007370:Interferon Type I; D007375:Interleukin-1; D008222:Lymphokines; C044162:leukoregulin; D007371:Interferon-gamma; D000212:Acyclovir