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Mutational analysis of the HIV-1 LTR as a promoter of negative sense transcription.

Bentley K, Deacon N, Sonza S, Zeichner S, Churchill M

  • Journal Archives of virology

  • Published 30 Aug 2004

  • Volume 149

  • ISSUE 12

  • Pagination 2277-94

  • DOI 10.1007/s00705-004-0386-8


The HIV-1 gene promoter is a bi-directional promoter of transcription. We report the characterization of the negative sense promoter (NSP) by analysis of the effect on negative sense transcription of a series of LTR U3 region substitution mutants. Mutations in the region nt -58 to -183 (positive sense transcription initiation nt +1) reduced transcription to <15% of wild type NSP activity. This region, essential for NSP activity, was designated the core basal promoter. Over expression of NF-kappaB RelA(p65) and LEF-1 increased negative sense expression, as did over expression of H-ras oncogene, consistent with the presence of cognate sequence motifs for NF-kappaB, LEF-1 and RBF. We were also able to confirm that the NSP is a TATA-less promoter inhibited by HIV-1 Tat. Based on our findings, we propose a model for the interaction between the NSP and PSP, and the role of Tat in regulating the interaction.