T. Mayhood et al., Inhibition of Tat-mediated transactivation of HIV-1 LTR transcription by polyamide nucleic acid targeted to TAR hairpin element, BIOCHEM, 39(38), 2000, pp. 11532-11539
Tar, an essential human immunodeficiency virus type 1 protein interacts wit
h the transactivation response element (TAR) and stimulates transcription f
rom the viral long-terminal repeat (LTR). Blockage of Tar-TAR interaction h
alts viral transcription and hence replication. We have found that polyamid
e nucleic acid (PNA), targeted to the TAR sequences of viral RNA genome is
able to prevent Tat-TAR interaction by efficient sequestration of the TAR.
Anti-TAR PNA competes for TAR and prevents Tat-mediated stimulation of HIV-
1 LTR transcription in vitro but has no influence on the basal level of tra
nscription in the absence of Tar. Using a reporter gene construct pHIV LTR-
CAT and pCMV-Tat in cell culture, we have further shown that anti-TAR PNA i
s able to block Tat-mediated transactivation of HIV-1 LTR transcription in
vivo as judged by the extent of LTR driven CAT gene expression in the absen
ce and presence of anti-TAR PNA. Supplementation of 100 nM of anti-TAR PNA
into the culture medium further enhances the suppression of transactivation
. Nonspecific scrambled PNA had no influence on Tar-TAR interaction and LTR
-driven CAT gene expression in cell culture. These results suggest that PNA
targeted to the TAR sequence of the viral genome may be a potential inhibi
tor of HIV-1 gene expression.