Human T-cell leukemia virus type-1 (HTLV-1) and human immunodeficiency virus (HIV) are retroviruses involved in different human diseases. However, following infection, these viruses inter into a latent state, rendering the infected individuals seropositive asymptomatic carriers. Although the pathogenic mechanisms of these viruses are not fully clear, the viral transactivators Tax and Tat proteins are widely regarded as a key elements in these mechanisms. However, during the latent period, viral gene expressions, including Tax or Tat genes, in the carrier’s infected cells is extremely low and bellow the pathogenically effective threshold. Therefore, it is conceivable that generating HTLV-1 or HIV related diseases would require an activation of the latent viruses. Thus, investigation of exogenous or intrinsic factors capable of initiating viral gene expression is of particular importance. Phorbol esters are exogeneous agents that have been shown to activate the expression of reporter genes driven by the long terminal repeat (LTR) of HTLV-1 and HIV. TPA, which belongs to phorbol esters, is a potent activator of protein kinase C (PKC). In the present study we examined involvement of the different PKC isoenzymes in the activation of reporter genes driven by both HTLV-1 and HIV LTRs. Our results proved that high activity of PKC-α and PKC-ε significantly prevented the activation of HTLV-1 LTR by treatment with TPA while high activity of these PKCs was required for the activation of HIV LTR. It seems that TPA induces the formation of SP1-p53 complex while active PKC induces the formation of SP1-p53-c-Jun tri-complex.
