Synergistic inhibition of Epstein-Barr virus: transformation of B lymphocytes by alpha and gamma interferon and by 3'-azido-3'-deoxythymidine. 1989

J C Lin, and Z X Zhang, and T C Chou, and I Sim, and J S Pagano
Lineberger Cancer Research Center, School of Medicine, University of North Carolina, Chapel Hill 27514.

We analyzed the effects of 3'-azido-3'deoxythymidine (AZT) and alpha and gamma interferon (IFN-alpha and IFN-gamma) on transformation of human umbilical cord lymphocytes (HUCLs) by Epstein-Barr virus (EBV). B lymphocytic outgrowth from HUCLs infected with EBV was monitored by focus formation; the presence of EBV genomes in transformed foci was confirmed by in situ cytohybridization and EBV nuclear antigen. The 50% inhibitory doses for preventing focus formation were 0.14 microM for AZT, 10 units (U)/mL for IFN-alpha, and 1 U/mL for IFN-gamma. To determine whether inhibition resulted from direct cytotoxic effects, we assessed the viability of nontransformed HUCLs exposed to the agents for 30 d. The nontoxic doses were 1 microM for AZT, 30 U/mL for IFN-alpha, and 3 U/mL for IFN-gamma. Combining IFN-alpha or IFN-gamma with AZT or IFN-alpha with IFN-gamma at nontoxic doses showed synergistic decreases in numbers of transformed foci. Transformation of HUCLs by EBV was sensitive to, but not abolished by, these agents at doses below those required for cell killing.

UI MeSH Term Description Entries
D007370 Interferon Type I Interferon secreted by leukocytes, fibroblasts, or lymphoblasts in response to viruses or interferon inducers other than mitogens, antigens, or allo-antigens. They include alpha- and beta-interferons (INTERFERON-ALPHA and INTERFERON-BETA). Interferons Type I,Type I Interferon,Type I Interferons,Interferon, Type I,Interferons, Type I
D007371 Interferon-gamma The major interferon produced by mitogenically or antigenically stimulated LYMPHOCYTES. It is structurally different from TYPE I INTERFERON and its major activity is immunoregulation. It has been implicated in the expression of CLASS II HISTOCOMPATIBILITY ANTIGENS in cells that do not normally produce them, leading to AUTOIMMUNE DISEASES. Interferon Type II,Interferon, Immune,gamma-Interferon,Interferon, gamma,Type II Interferon,Immune Interferon,Interferon, Type II
D002470 Cell Survival The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. Cell Viability,Cell Viabilities,Survival, Cell,Viabilities, Cell,Viability, Cell
D002472 Cell Transformation, Viral An inheritable change in cells manifested by changes in cell division and growth and alterations in cell surface properties. It is induced by infection with a transforming virus. Transformation, Viral Cell,Viral Cell Transformation,Cell Transformations, Viral,Transformations, Viral Cell,Viral Cell Transformations
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004357 Drug Synergism The action of a drug in promoting or enhancing the effectiveness of another drug. Drug Potentiation,Drug Augmentation,Augmentation, Drug,Augmentations, Drug,Drug Augmentations,Drug Potentiations,Drug Synergisms,Potentiation, Drug,Potentiations, Drug,Synergism, Drug,Synergisms, Drug
D004854 Herpesvirus 4, Human The type species of LYMPHOCRYPTOVIRUS, subfamily GAMMAHERPESVIRINAE, infecting B-cells in humans. It is thought to be the causative agent of INFECTIOUS MONONUCLEOSIS and is strongly associated with oral hairy leukoplakia (LEUKOPLAKIA, HAIRY;), BURKITT LYMPHOMA; and other malignancies. Burkitt Herpesvirus,Burkitt Lymphoma Virus,E-B Virus,EBV,Epstein-Barr Virus,Human Herpesvirus 4,Infectious Mononucleosis Virus,Burkitt's Lymphoma Virus,HHV-4,Herpesvirus 4 (gamma), Human,Burkitts Lymphoma Virus,E B Virus,E-B Viruses,Epstein Barr Virus,Herpesvirus, Burkitt,Infectious Mononucleosis Viruses,Lymphoma Virus, Burkitt,Mononucleosis Virus, Infectious,Mononucleosis Viruses, Infectious
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D001402 B-Lymphocytes Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation. B-Cells, Lymphocyte,B-Lymphocyte,Bursa-Dependent Lymphocytes,B Cells, Lymphocyte,B Lymphocyte,B Lymphocytes,B-Cell, Lymphocyte,Bursa Dependent Lymphocytes,Bursa-Dependent Lymphocyte,Lymphocyte B-Cell,Lymphocyte B-Cells,Lymphocyte, Bursa-Dependent,Lymphocytes, Bursa-Dependent

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