Negative-strand RNA transcripts are produced in human immunodeficiency virus type 1-infected cells and patients by a novel promoter downregulated by Tat

Nelson L. Michael*, Maryanne T. Vahey, Lisa D'Arcy, Philip K. Ehrenberg, Joseph D. Mosca, Jay Rappaport, Robert R. Redfield

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

78 Scopus citations

Abstract

Current understanding of human immunodeficiency virus type 1 (HIV-1) transcription is based on unidirectional expression of transcripts with positive-strand polarity from the 5' long terminal repeat. We now report HIV- 1 transcripts with negative-strand polarity obtained from acutely and chronically infected cell lines by use of a template orientation-specific reverse transcriptase-PCR assay. These findings were confirmed in natural infection by analysis of RNA derived from peripheral blood mononuclear cell samples from 15 HIV-1-infected patients. A cDNA derived from a 2.3-kb polyadenylated HIV-1 RNA with negative-strand polarity which encodes a highly conserved 189-amino-acid open reading frame antiparallel to the envelope gene was isolated from acutely infected A3.01 cells. Through use of reporter gene constructions, we further found that a novel negative-strand promoter functions within the negative response element of the 3' long terminal repeat, which is downregulated by coexpression of Tat. Site-directed mutagenesis experiments demonstrated that NF-κB I and USF sites are crucial for negative-strand promoter activity. These data extend the coding capacity of HIV-1 and suggest a role for antisense regulation of the viral life cycle.

Original languageEnglish
Pages (from-to)979-987
Number of pages9
JournalJournal of Virology
Volume68
Issue number2
DOIs
StatePublished - Feb 1994
Externally publishedYes

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