NITRIC-OXIDE PRODUCED BY HUMAN B-LYMPHOCYTES INHIBITS APOPTOSIS AND EPSTEIN-BARR-VIRUS REACTIVATION
NITRIC-OXIDE PRODUCED BY HUMAN B-LYMPHOCYTES INHIBITS APOPTOSIS AND EPSTEIN-BARR-VIRUS REACTIVATION
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DOI：
10.1016/0092-8674(94)90005-1
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发表时间：
1994-12-30
期刊：
影响因子：
64.5
通讯作者：
STAMLER, JS
中科院分区：
文献类型：
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作者：
MANNICK, JB;ASANO, K;STAMLER, JS
由鼠巨噬细胞产生的一氧化氮（NO）在鼠对肢脱病病毒、单纯疱疹病毒和牛痘病毒感染的抵抗中是重要的。相比之下，人单核细胞的NO产生一直难以证明，NO在人类对感染的反应中的作用是不确定的。我们报告组成，低水平，巨噬细胞型NO合酶（iNOS）的表达在EB病毒（EBV）转化的人B淋巴细胞和伯基特淋巴瘤细胞系。免疫NOS活性通过下调即刻早期EBV反式激活因子Zta的表达参与维持EBV潜伏期。NO还抑制B淋巴细胞系的凋亡。NO的作用在很大程度上不依赖于cGMP，并影响由（巯基）氧化还原状态调节的信号通路。这些结果表明，NO通过抑制程序性细胞死亡和维持病毒潜伏期在人类细胞生物学中发挥生理作用。
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 a cell biology by inhibiting programmed cell death and maintaining viral latency.