Human immunodeficiency virus type 1 transcription is regulated by thieno[3,4-d]pyrimidine

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 mu M 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-alpha 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-kappa B pathway. Therefore, TEP may be used for the treatment of HIV-1 infection.