Rapid activation and subsequent down-regulation of the human immunodeficiency virus type 1 promoter in the presence of Tat: possible mechanisms contributing to latency

J Virol. 1991 Jun;65(6):3044-51. doi: 10.1128/JVI.65.6.3044-3051.1991.

Abstract

The mechanism of induction of gene expression of the human immunodeficiency virus type 1 long terminal repeat (LTR) by the Tat transactivator protein was studied in a cell fusion assay. Tat causes a rapid activation of both transcription from the LTR and accumulation of hybrid LTR-chloramphenicol acetyltransferase mRNAs. Approximately 4 h after induction by Tat, expression from the LTR promoter is down-regulated, resulting in a decrease in the accumulation of LTR mRNA. This down-regulation of expression occurs in the continued presence of Tat. Protein synthesis inhibitors can block this down-regulation; therefore, the postinduction repression of expression is dependent upon de novo protein synthesis. We propose that a labile cellular protein(s) is responsible for the low levels of human immunodeficiency virus type 1 expression, possibly contributing to the establishment of a latent state of viral expression.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Cell Line
  • Chloramphenicol O-Acetyltransferase / genetics
  • Down-Regulation*
  • Gene Products, tat / biosynthesis
  • Gene Products, tat / genetics*
  • HIV Long Terminal Repeat
  • HIV-1 / genetics*
  • HeLa Cells / microbiology
  • Humans
  • Kinetics
  • Promoter Regions, Genetic*
  • RNA, Messenger / metabolism
  • Transcription, Genetic
  • tat Gene Products, Human Immunodeficiency Virus

Substances

  • Gene Products, tat
  • RNA, Messenger
  • tat Gene Products, Human Immunodeficiency Virus
  • Chloramphenicol O-Acetyltransferase