Lu Y C, Touzjian N, Stenzel M, Dorfman T, Sodroski J G, Haseltine W A
Dana-Farber Cancer Institute, Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115.
J Acquir Immune Defic Syndr (1988). 1991;4(2):173-7.
The rate of transcription initiation directed by the long terminal repeat (LTR) of HIV-1 increases in response to mitogenic stimuli of T cells. Here we show that the response of the HIV-1 LTR may be governed by two independent sequences located 5' to the site of transcription initiation sequences that bind either NFAT-1 or NF kappa B. The rate of LTR-directed gene expression increased in response to treatment with either a phorbol ester or tumor necrosis factor alpha if either the NFAT-1 or NF kappa B binding sites were deleted, but failed to respond to these mitogenic stimuli if both sequences were absent. The HIV-1 mutant virus containing both NF kappa B and NFAT-1 deletion was able to replicate although at a much decreased growth rate, while the deletion of NFAT-1 alone increased the viral growth rate in Jurkat cells. Neither deletion of NF kappa B nor deletion of NFAT-1 decreased activation of viral replication by phorbol ester.
HIV-1长末端重复序列（LTR）指导的转录起始速率会随着T细胞的促有丝分裂刺激而增加。我们在此表明，HIV-1 LTR的反应可能受位于转录起始序列位点5'端的两个独立序列调控，这两个序列分别结合NFAT-1或NF-κB。如果NFAT-1或NF-κB结合位点被删除，LTR指导的基因表达速率会因佛波酯或肿瘤坏死因子α处理而增加，但如果两个序列都缺失，则对这些促有丝分裂刺激无反应。同时缺失NF-κB和NFAT-1的HIV-1突变病毒虽能复制，但其生长速率大幅降低，而单独缺失NFAT-1则会增加病毒在Jurkat细胞中的生长速率。NF-κB的缺失或NFAT-1的缺失均未降低佛波酯对病毒复制的激活作用。
