Mannick J B, Asano K, Izumi K, Kieff E, Stamler J S
Department of Microbiology and Molecular Genetics, Harvard Medical School, Brigham and Women's Hospital, Boston, Massachusetts 02115.
Cell. 1994 Dec 30;79(7):1137-46. doi: 10.1016/0092-8674(94)90005-1.
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.
小鼠巨噬细胞产生的一氧化氮（NO）在小鼠抵抗痘苗病毒、单纯疱疹病毒和埃可病毒感染中起重要作用。相比之下，人类单核细胞产生NO的情况很难得到证实，而且NO在人类感染反应中的作用尚不确定。我们报告了在爱泼斯坦-巴尔病毒（EBV）转化的人类B淋巴细胞和伯基特淋巴瘤细胞系中组成性、低水平的巨噬细胞型一氧化氮合酶（iNOS）表达。免疫NOS活性通过下调EBV早期即刻反式激活因子Zta的表达参与维持EBV潜伏状态。NO还可抑制B淋巴细胞系中的细胞凋亡。NO的作用在很大程度上不依赖于环磷酸鸟苷（cGMP），并且对由（巯基）氧化还原状态调节的信号通路有影响。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状态在人类B细胞生物学中发挥生理作用。
