Xu Wenfang, Wu Yong, Zhao Jiaoping, Chen Jiangnan, Zhang Weiyang
Clinical Laboratory, Shaoxing Municipal Hospital, Shaoxing, Zhejiang 312000, P.R. China.
Medical Department, Shaoxing Municipal Hospital, Shaoxing, Zhejiang 312000, P.R. China.
Exp Ther Med. 2020 Apr;19(4):3090-3096. doi: 10.3892/etm.2020.8532. Epub 2020 Feb 18.
In the present study, the effect of thieno[3,4-]pyrimidine (TEP) on the transcription of human immunodeficiency virus type 1 (HIV-1) was investigated. To the best of the authors' knowledge, this is the first study describing the effect of TEP on the transcription of HIV-1. The present results identified a marked decrease in the production of the HIV-1 genome in 293T cells after treatment with TEP. The treatment of HIV-1infected 293T cells with TEP led to the upregulation of retinoblastoma binding protein 4 (RbAp48) mRNA and protein. The activity of long terminal repeats (LTRs) was decreased by 19, 24, 29, 34, 38, 41, 52, 63, 76 and 92% in treatments with concentrations of 0.25, 0.5, 0.75, 1.0, 1.25, 1.5, 1.75, 2.0, 2.25 and 2.5 µM TEP, respectively. The p65 translocation to the nucleus was markedly reduced in 293T cells treated with TEP for 48 h. A marked decrease was observed in the production of HIV-1 in 293T cells with the increase in concentration of pRbAp48. In 293T cells, RbAp48 and TEP decreased tumor necrosis factor-α and phorbol 12-myristate 13-acetate-induced activity of LTR. Therefore, the present study suggested that TEP inhibited transcription of HIV-1 through upregulation of RbAp48 expression and activation of the NF-κB pathway. Therefore, TEP may be used for the treatment of HIV-1 infection.
在本研究中，研究了噻吩并[3,4 - ]嘧啶（TEP）对1型人类免疫缺陷病毒（HIV - 1）转录的影响。据作者所知，这是第一项描述TEP对HIV - 1转录影响的研究。目前的结果表明，用TEP处理后，293T细胞中HIV - 1基因组的产生显著减少。用TEP处理HIV - 1感染的293T细胞导致视网膜母细胞瘤结合蛋白4（RbAp48）mRNA和蛋白上调。在分别用浓度为0.25、0.5、0.75、1.0、1.25、1.5、1.75、2.0、2.25和2.5 μM的TEP处理时，长末端重复序列（LTR）的活性分别降低了19%、24%、29%、34%、38%、41%、52%、63%、76%和92%。在用TEP处理48小时的293T细胞中，p65向细胞核的转位明显减少。随着pRbAp48浓度的增加，293T细胞中HIV - 1的产生显著减少。在293T细胞中，RbAp48和TEP降低了肿瘤坏死因子-α和佛波酯12 - 肉豆蔻酸酯13 - 乙酸酯诱导的LTR活性。因此，本研究表明TEP通过上调RbAp48表达和激活NF - κB途径抑制HIV - 1转录。因此，TEP可用于治疗HIV - 1感染。
