Altman R, Harrich D, Garcia J A, Gaynor R B
Department of Medicine, University of California, Los Angeles School of Medicine 90024.
J Virol. 1988 Apr;62(4):1339-46. doi: 10.1128/JVI.62.4.1339-1346.1988.
Human T-cell leukemia virus types I (HTLV-I) and II (HTLV-II) are human retroviruses which normally infect T-lymphoid cells. HTLV-I infection is associated with adult T-cell leukemia-lymphoma, and HTLV-II is associated with an indolent form of hairy-cell leukemia. To identify potential transcriptional regulatory elements of these two related human retroviruses, we performed DNase I footprinting of both the HTLV-I and HTLV-II long terminal repeats (LTRs) by using extracts prepared from uninfected T cells, HTLV-I and HTLV-II transformed T cells, and HeLa cells. Five regions of the HTLV-I LTR and three regions of the HTLV-II LTR showed protection by DNase I footprinting. All three of the 21-base-pair repeats previously shown to be important in HTLV transcriptional regulation were protected in the HTLV-I LTR, whereas only one of these repeats was protected in the HTLV-II LTR. Several regions exhibited altered protection in extracts prepared from lymphoid cells as compared with HeLa cells, but there were minimal differences in the protection patterns between HTLV-infected and uninfected lymphoid extracts. A number of HTLV-I and HTLV-II LTR fragments which contained regions showing protection in DNase I footprinting were able to function as inducible enhancer elements in transient CAT gene expression assays in the presence of the HTLV-II tat protein. The alterations in the pattern of the cellular proteins which bind to the HTLV-I and HTLV-II LTRs may in part be responsible for differences in the transcriptional regulation of these two related viruses.
人类T细胞白血病病毒I型(HTLV-I)和II型(HTLV-II)是通常感染T淋巴细胞的人类逆转录病毒。HTLV-I感染与成人T细胞白血病-淋巴瘤相关,而HTLV-II与一种惰性形式的毛细胞白血病相关。为了鉴定这两种相关人类逆转录病毒的潜在转录调控元件,我们通过使用从未感染的T细胞、HTLV-I和HTLV-II转化的T细胞以及HeLa细胞制备的提取物,对HTLV-I和HTLV-II的长末端重复序列(LTRs)进行了DNase I足迹分析。HTLV-I LTR的五个区域和HTLV-II LTR的三个区域在DNase I足迹分析中显示出受保护。先前显示在HTLV转录调控中重要的21个碱基对重复序列中的所有三个在HTLV-I LTR中都受到保护,而在HTLV-II LTR中仅其中一个重复序列受到保护。与HeLa细胞相比,几个区域在从淋巴细胞制备的提取物中表现出改变的保护,但在HTLV感染和未感染的淋巴细胞提取物之间的保护模式差异最小。许多包含在DNase I足迹分析中显示受保护区域的HTLV-I和HTLV-II LTR片段在HTLV-II tat蛋白存在的情况下,能够在瞬时CAT基因表达测定中作为可诱导的增强子元件发挥作用。与HTLV-I和HTLV-II LTR结合的细胞蛋白模式的改变可能部分负责这两种相关病毒转录调控的差异。