Effects of HIV-1 Tat on expression of HLA class I molecules.

Effects of HIV-1 Tat on expression of HLA class I molecules.
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DOI:
10.1097/00042560-199603010-00003
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发表时间:
1996-03
期刊:
Journal of acquired immune deficiency syndromes and human retrovirology : official publication of the International Retrovirology Association
影响因子:
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通讯作者:
M. Matsui;R. Warburton;P. Cogswell;A. Baldwin;J. Frelinger
M. Matsui;R. Warburton;P. Cogswell;A. Baldwin;J. Frelinger
中科院分区:
其他
文献类型:
--
作者:
M. Matsui;R. Warburton;P. Cogswell;A. Baldwin;J. Frelinger

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HIV-1的达特蛋白是一种有效的转录反式激活因子,是HIV-1复制所必需的。此外,达特被认为具有免疫抑制功能,这表明达特可能在与艾滋病相关的免疫功能障碍中发挥直接作用。最近,已经报道达特抑制主要组织相容性复合体(MHC)I类基因启动子的活性。由于HIV感染下调I类分子的表达,该数据强烈提示达特下调I类分子的表达并导致CTL活性的丧失。在这里,我们报告的影响,达特对I类表达使用人细胞系,T0,表达达特(TO-达特)。北方印迹分析显示,T0-达特中MHC I类转录物的水平正常。流式细胞术分析表明,在T0-达特中,达特基本上不下调HLA I类分子的表达到任何大的程度。此外,继之以内切糖基化酶-H处理的脉冲追踪实验表明,T0-达特中I类分子的成熟和加工速率与原始细胞系T0中的I类分子的成熟和加工速率没有区别。总之,这些数据表明达特表达不一定导致I类表达下调。
Tat protein of HIV-1 is a potent transactivator of transcription and essential for HIV-1 replication. In addition, Tat has been proposed to possess immunosuppressive functions, suggesting that Tat may play a direct role in the immune dysfunction associated with AIDS. Recently, it has been reported that Tat represses activity of a major histocompatibility complex (MHC) class I gene promoter. Because HIV infection downmodulates expression of class I molecules, this data strongly suggests that Tat downregulates class I expression and leads to loss of CTL activity. Here, we report effects of Tat on class I expression using a human cell line, T0, expressing Tat (TO-Tat). Northern blot analysis shows that levels of MHC class I transcripts are normal in T0-Tat. Flow cytometry analyses indicate that expression of HLA class I molecules is not substantially downregulated to any great extent by Tat in T0-Tat. Further, pulse-chase experiments followed by Endoglycosidase-H treatment show that the rate of maturation and processing of class I molecules in T0-Tat is indistinguishable from that in the original cell line, T0. Taken together, these data suggest that Tat expression does not necessarily result in downregulation of class I expression.