HIV-MEDIATED REPRESSION OF MHC CLASS I GENE EXPRESSION

MHC-I类分子是病毒多肽的主要受体， 作为特定细胞毒性T淋巴细胞的靶点。HIV-1 UP特异性降低MHC-I类基因启动子的活性 增加到12倍。抑制是由HIV-1Tat蛋白介导的 从剪接的病毒转录本(双外显子TAT)中，识别出一本小说 双外显子TAT的活性，不同于TAT的反式激活 单外显子和双外显子TAT共有的HIV LTR。纹身压抑阶级 通过与班级的直接互动抄写 推动者。TAT抑制可以由强大的上游调节 增强剂元素。 TAT蛋白功能结构域的图谱表明 抑制和激活是由不同的和可分离的 域名。第二个外显子的精细图谱定位了一个片段 在80到86个氨基酸之间，是抑制所必需的。 此外，57到67岁之间的富含谷氨酰胺的区域似乎也 参与调停镇压。半胱氨酸的消除- 转录激活所必需的丰富结构域不会被废除 压抑。然而，一个中心残基被证明是必要的 TAT与TBP的相互作用是反式激活和 压抑。

MHC Class I molecules are the major receptors for viral peptides and serve as targets for specific cytotoxic T lymphocytes. HIV-1 specifically decreased activity of an MHC class I gene promoter by up to 12-fold. Repression is mediated by the HIV-1 Tat protein derived from a spliced viral transcript (two-exon Tat), identifying a novel activity for two-exon Tat, distinct from the transactivation of the HIV LTR common to both one-exon and two-exon Tat. Tat represses class I transcription through a direct interaction with the class I promoter. Tat repression can be modulated by strong, upstream enhancer elements. Mapping of functional domains of the Tat protein demonstrates that repression and activation are mediated by distinct and separable domains. Fine mapping of the second exon has localized a segment between amino acids 80 and 86 as essential for repression. Furthermore, a glutamine-rich domain, between 57 and 67 also seems to participate in mediating repression. Elimination of the cysteine- rich domain which is necessary for transactivation does not abrogate repression. However, a central residue shown to be necessary for the interaction of Tat with TBP is necessary for both transactivation and repression.