Virology. 1997 Jun 9;232(2):337-44. Unique Identifier : AIDSLINE
The LTRs of HIV-1 and HTLV-I have been shown by several laboratories to
be activated by 12-O-tetradecanoylphorbol-13-acetate (TPA). This agent
is a potent activator of protein kinase C (PKC). However, long exposure
to TPA downregulates PKC in many cell types. We demonstrated that TPA
treatment of Jurkat cells for more than 24 hr resulted in a sever
depletion of this enzyme. Therefore, to explore the role of PKC in the
effect of TPA on these LTRs, we transfected Jurkat cells with HIV-1
LTR-CAT or HTLV-I LTR-CAT construct after 72 hr of TPA pretreatment.
While this TPA pretreatment considerably reduced the HIV-1 LTR basal
expression, it strongly stimulated the expression of HTLV-I LTR.
Furthermore, when TPA was added after transfection, a strong stimulation
of HIV-1 LTR was observed, which could be abrogated by PKC inhibitors
like H7 and chelerythryn. However, under these conditions TPA stimulated
HTLV-I LTR to a lesser extent than did the long-term TPA pretreatment.
Moreover, this stimulation was enhanced by the PKC inhibitors. Thus our
data indicate that while the effect of TPA on HIV-1 LTR is strictly
dependent on PKC activity, its effect on HTLV-I LTR is exerted via a
different pathway that not only does not require PKC activation but
rather seems to be antagonized by the activated PKC. Using a deletion
mutant of HTLV-I LTR we mapped the PKC-independent effect of TPA to the
c-ets responsive region 1 (ERR-1) located in U3 of this LTR.
*Gene Expression Regulation, Viral/DRUG EFFECTS *HIV Long Terminal
Repeat *HIV-1/GENETICS *HTLV-I/GENETICS *Protein Kinase C/METABOLISM
*Repetitive Sequences, Nucleic Acid *Tetradecanoylphorbol