Nitric oxide produced by human B lymphocytes inhibits apoptosis and Epstein-Barr virus reactivation.
Nitric oxide (NO) produced by murine macrophages is important in murine resistance to ectromelia virus, herpes simplex virus, and vaccinia virus infection. In contrast, NO production by human mononuclear cells has been difficult to demonstrate, and a role for NO in human responses to infection is uncertain. We report constitutive, low level, macrophage-type NO synthase (iNOS) expression in Epstein-Barr virus (EBV)-transformed human B lymphocytes and Burkitt's lymphoma cell lines. Immune NOS activity is involved in maintaining EBV latency through down-regulation of the expression of the immediate-early EBV transactivator Zta. NO also inhibits apoptosis in B lymphocyte cell lines. The effects of NO are largely independent of cGMP and influential on signaling pathways regulated by (sulfhydryl) redox status. These results suggest that NO plays a physiological role in human B cell biology by inhibiting programmed cell death and maintaining viral latency.
Mannick
J B
JB
Department of Microbiology and Molecular Genetics, Harvard Medical School, Brigham and Women's Hospital, Boston, Massachusetts 02115.
Asano
K
K
Izumi
K
K
Kieff
E
E
Stamler
J S
JS
D000328:Adult; D000594:Amino Acid Oxidoreductases / Q000378:metabolism; D017209:Apoptosis / Q000502:physiology*; D001402:B-Lymphocytes / Q000276:immunology / Q000502:physiology* / Q000821:virology; D001483:Base Sequence; D002461:Cell Line, Transformed; D004854:Herpesvirus 4, Human / Q000254:growth & development* / Q000276:immunology; D006801:Humans; D007231:Infant, Newborn; D008969:Molecular Sequence Data; D009569:Nitric Oxide / Q000096:biosynthesis / Q000502:physiology*; D019001:Nitric Oxide Synthase; D014407:Tumor Cells, Cultured; D014775:Virus Activation / Q000276:immunology*
D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases