Abstract
In the present study, the effect of thieno[3,4-d]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.
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