REGULATION OF VIRAL AND CELLULAR GENE EXPRESSON

人嗜T淋巴细胞病毒I型（HTLV-1）编码一个40 kD的核内 反式激活磷蛋白Tax 1。 通过与细胞的相互作用 Tax 1是一种转录因子，它调节病毒和细胞的水平。 基因表达。 体外反式激活测定，其中野生型Tax 1 能够反式激活HTLV-1启动子或异源启动子 包含Tax 1响应元素的。 的in 体外系统利用HTLV-I 21个碱基对重复克隆的上游， 卵清蛋白启动子和无G盒。 纯化的Tax 1特异性 反式激活这个模板5到10倍， 依赖的方式。 反式激活被有效地中和， 抗Tax 1血清，而非对照血清。 转录被低浓度的 α-鹅膏蕈碱的浓度。 卵清蛋白无反式激活 观察到启动子模板对照。 与体内一致 反式激活活性，Tax 1突变体M22（CREB突变体），但无M47 （NF-κ B突变体），反式激活含有串联21 碱基对重复 在重组的体外转录测定中，Tax 1 反式激活依赖于基础转录因子TFIID， TFIIA。 TBP在功能上不能替代TFIID， 反式激活测定。 HTLV-I长末端的Tax 1反式激活 重复序列（LTR）也已在体外进行了检查。 在全细胞提取物中， Tax 1反式激活HTLV-I LTR，但不激活HIV LTR模板。 两 HTLV-I LTR的基础和Tax 1反式激活的转录活性 对低浓度的鹅膏蕈碱有抵抗力 人类疱疹病毒6型（HHV-6）是一种嗜淋巴细胞病毒， 淋巴组织增生性疾病患者的外周血淋巴细胞（PBL） 紊乱 HHV-6 DNA序列已在许多人中鉴定， 恶性肿瘤，包括非洲伯基特淋巴瘤和EB病毒 (EBV)阴性B细胞淋巴瘤。 HHV-6也可能是HHV-1的辅因子。 艾滋病的进展。 HHV-6 Sal 1-L ORF-1与HHV-6 Sal 1-L ORF-1的同源性为100%。 开放阅读框编码357个氨基酸的蛋白质，其反式激活 HIV LTR。

Human T-cell lymphotropic virus type I (HTLV-I) encodes a 40 kD nuclear transactivating phosphoprotein, Tax1. Through interaction with cellular transcription factors, Tax1 regulates the level of viral and cellular gene expression. An in vitro transactivation assay, where wild type Tax1 is able to transactivate the HTLV-I promoter or a heterologous promoter that contains the Tax1 responsive elements, has been developed. The in vitro system utilizes the HTLV-I 21 base pair repeats cloned upstream of the ovalbumin promoter and G-free cassette. Purified Tax1 specifical ly transactivates this template five-to ten-fold in a concentration- dependent manner. Transactivation was effectively neutralized by anti-Tax1, but not control, sera. Transcription was inhibited by low concentrations of alpha-amanitin. No transactivation of the ovalbumin promoter template control was observed. Consistent with in vivo transactivating activity, Tax1 mutant M22 (CREB mutant) but not M47 (NF-kappaB mutant), transactivated the template containing the tandem 21 base pair repeat. In a reconstituted in vitro transcription assay, Tax1 transactivation was dependent upon basal transcription factors TFIID and TFIIA. TBP did not functionally substitute for TFIID in the transactivation assay. Tax1 transactivation of the HTLV-I long terminal repeat (LTR) has also been examined in vitro. In whole cell extracts, Tax1 transactivated the HTLV-I LTR but not the HIV LTR template. Both basal and Tax1-transactivated transcriptional activity of the HTLV-I LTR were resistant to low concentrations of alpha-amanitin. Human herpesvirus type 6 (HHV-6) is a lymphotropic virus isolated from peripheral blood lymphocytes (PBLs) of patients with lymphoproliferative disorders. HHV-6 DNA sequences have been identified in a number of human malignancies including African Burkitt's lymphoma and Epstein-Barr virus (EBV) negative B-cell lymphomas. HHV-6 may also be a cofactor in the progression of AIDS. It was demonstrated that the HHV-6 Sal1-L ORF-1 open reading frame encodes a 357 amino acid protein which transactivates the HIV LTR.