MOLECULAR MECHANISM OF IFN-Y INDUCTION AND ACTIVITY

我们最近报道了两个EB病毒转化的人类细胞系， 暴露在热休克条件下，产生一种抗病毒活性。这 其活性被表征为干扰素-伽玛(干扰素-伽玛)。其中之一 这些细胞系GM3299从构成上产生高水平的干扰素-α， 而GM4408产生的干扰素-α非常少(如果有的话)。首字母 对产生的干扰素-α的表征表明有可能 这是一种不同于PHA刺激的T淋巴细胞的干扰素 干扰素-伽玛。GM3299细胞诱导的极高水平的干扰素活性 热休克可能反映了干扰素和α-干扰素之间的增强或协同作用 干扰素-伽玛。我们将提纯并鉴定这种“新颖的”干扰素。我们 将详细描述诱导过程并克隆干扰素-γ 吉恩。我们将尝试定义涉及到的核苷酸序列 “热感应。”使用克隆的EB病毒DNA片段，我们将检查 EB DNA合成和转录之间的关系，以及 干扰素诱导过程。这些实验将与In并行 发热对干扰素诱导影响的体内研究。 我们已经测量了感染生殖器疱疹的干扰素水平。 病人。在血清中检测到高水平的干扰素-α和干扰素-β 在疱疹小泡中。PHA刺激的淋巴细胞产生10-100倍以上 干扰素-γ对对照组淋巴细胞的刺激作用。与…相反 其他报道称，干扰素-伽玛可抑制培养中疱疹病毒斑块的形成。 干扰素-α和干扰素-β活性较低。我们将研究分子 这是使用克隆的HSV基因的抗病毒活性的基础。 最近的报道表明，小鼠干扰素-γ与 巨噬细胞激活因子。这将进行人类干扰素-伽马的检查 使用单抗。我们将尝试在功能上将 干扰素-γ的三大功能：抗病毒、抗增殖和 巨噬细胞激活。

We have recently reported that two EB virus-transformed human cell lines, on exposure to heat shock conditions, produce an antiviral activity. This activity has been characterized as interferon-Gamma (IFN-Gamma). One of the cell lines, GM3299, produces high levels of IFN-Alpha constitutively, whereas GM4408 produces very little (if any) IFN-Alpha. Initial characterization of the IFN-Alpha produced indicates the possibility that this is a species of interferon differing from PHA-stimulated T-lymphocyte IFN-Gamma. The very high levels of interferon activity induced in GM3299 by heat shock may reflect potentiation or synergism between IFN-Alpha and IFN-Gamma. We shall purify and characterize this 'novel' interferon. We shall characterize the induction process in detail and clone the IFN-Gamma gene. We shall attempt to define the nucleotide sequences involved in "heat-induction." Using cloned EB virus DNA segments, we shall examine the relationship, if any, between EB DNA synthesis and transcription and the interferon induction process. These experiments will be paralleled with in vivo studies on the effect of fever on interferon induction. We have measured the interferon levels in genital herpes-infected patients. High levels of IFN-Alpha are detected in the serum, and IFN-Beta in herpatic vesicles. PHA-stimulated lymphocytes produce 10-100 times more IFN-Gamma than stimulated lymphocytes of control individuals. Contrary to other reports, IFN-Gamma inhibits herpes plaque formation in culture. IFN-Alpha and IFN-Beta are less active. We shall examine the molecular basis of this antiviral activity of using cloned HSV genes. Recent reports indicate that murine IFN-Gamma is identical to macrophage-activating factor. This will be examined for human IFN-Gamma using monoclonal antibodies. We shall attempt to functionally separate the three functions of IFN-Gamma: antiviral, anti-proliferative, and macrophage activation.