Inhibition of tat-mediated transactivation of HIV-1 LTR transcription by polyamide nucleic acid targeted to TAR hairpin element

T. Mayhood, N. Kaushik, P. K. Pandey, F. Kashanchi, L. Deng, V. N. Pandey

Research output: Contribution to journalArticlepeer-review

59 Scopus citations

Abstract

Tat, an essential human immunodeficiency virus type 1 protein interacts with the transactivation response element (TAR) and stimulates transcription from the viral long-terminal repeat (LTR). Blockage of Tat-TAR interaction halts viral transcription and hence replication. We have found that polyamide 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 transcription in the absence of Tat. Using a reporter gene construct pHIV LTR-CAT and pCMV-Tat in cell culture, we have further shown that anti-TAR PNA is 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 absence 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 Tat-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 inhibitor of HIV-1 gene expression.

Original languageEnglish (US)
Pages (from-to)11532-11539
Number of pages8
JournalBiochemistry
Volume39
Issue number38
DOIs
StatePublished - Sep 26 2000

All Science Journal Classification (ASJC) codes

  • Biochemistry

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