HTLV-III SEQUENCES AT THE TRANSCRIPTIONAL LEVEL

寄生虫性病毒感染在以下患者中普遍存在： 获得性免疫缺陷综合症（艾滋病）。 探讨 疱疹病毒群中的机会性感染 可能诱导人类T淋巴细胞病毒表达 III型（HTLV-III）长末端重复序列（LTR），我们构建了 永久性细胞系（鼠和猿），含有HTLV-III 指导氯霉素乙酰转移酶（CAT）基因的LTR。 而在瞬时基因表达试验中，HTLV-III LTR 表达CAT活性与猴病毒40（SV 40）一样高， 启动子，染色质后没有观察到CAT活性 在永久细胞系中的整合。 这些潜伏的 含有疱疹病毒的HTLV-III LTR的细胞系重新激活了 通过S1核酸酶RNA分析测定的HTLV-III LTR。 而猴病毒-40（SV 40）和腺病毒感染 含有潜伏的HTLV-III LTR的细胞系不激活HTLV。 III LTR表达。 潜伏性HTLV-III LTR的再活化 转录也观察到后5氮杂胞苷，放线菌酮 和UV照射处理。 在分离的 核，表明激活是在转录水平上。 单纯疱疹病毒1型（HSV-1）的激活需要病毒 通过病毒测定立即早期（IE）基因表达 放线菌酮存在下的感染和突变体 病毒基因表达缺陷。 的长期目标 本提案中描述的研究旨在阐明 HTLV-III LTR可被激活的机制 转录水平。 具体目标是确定 负责潜伏性HTLV-III LTR的病毒基因产物 转录激活;建立永久的细胞系， 含有HTLV-III LTR的人B和T细胞; 抑制HTLV-III调节区的机制， 为了确定涉及抑制的HTLV-III LTR DNA序列， 和重新激活。 初步结果表明， 疱疹病毒组的机会性感染可诱导 HTLV-III在潜伏感染中携带病毒的个体中的表达 形式，并指出这些细胞系的潜力，以研究 其他理化刺激对HTLV-III再活化的影响。

Opportunistic viral infections are prevalent in patients with acquired immune deficiency syndrome (AIDS). To investigate the possibility that opportunistic infections in the herpesvirus group might induce expression from the human T-lymphotropic virus type III (HTLV-III) long-terminal repeats (LTR), we constructed permanent cell lines (murine and simian), containing the HTLV-III LTR directing the chloramphenicol acetyltransferase (CAT) gene. Whereas in transient gene expression assays, the HTLV-III LTR express CAT activity as high as the simian virus-40 (SV40) early promoter, no CAT activity is observed after chromatin integration in permanent cell lines. Superinfection of these latent HTLV-III LTR containing lines with herpes viruses reactivated the HTLV-III LTR as determined by S1 nuclease RNA analysis. Whereas simian virus-40 (SV40) and adenovirus infection of the latent HTLV-III LTR containing cell lines did not activate HTLV- III LTR expression. Reactivation of latent HTLV-III LTR transcription is also observed after 5 azacytidine, cycloheximide and UV irradiation treatments. Run-on transcription in isolated nuclei, suggests that the activation is on the transcriptional level. Activation by herpes simplex virus type 1 (HSV-1) required viral immediate early (IE) gene expression as determined by virus infection in the presence of cycloheximide and with mutants defective in viral gene expression. The long-term objective of the research described in this proposal is to elucidate the mechanism(s) by which the HTLV-III LTR could be activated on the transcriptional level. The specific aims are to identify the viral gene products responsible for latent HTLV-III LTR transcription activation; to establish permanent cell lines in human B and T-cells containing the HTLV-III LTR; to identify the mechanism(s) of repression of the HTLV-III regulatory region and to define the HTLV-III LTR DNA sequences involved repression and reactivation. The preliminary results suggest that opportunistic infection of the herpesvirus group could induce HTLV-III expression in individuals harboring the virus in a latent form and points to the potential of these cell lines to study the affects of other physiochemical stimuli on HTLV-III reactivation.