Rapid activation and subsequent down-regulation of the human immunodeficiency virus type 1 promoter in the presence of Tat: possible mechanisms contributing to latency.
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.
Drysdale
C M
CM
National Cancer Institute-Frederick Cancer Research and Development Center, ABL-Basic Research Program, Maryland 21702-1201.
Pavlakis
G N
GN
D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D015536:Down-Regulation; D015696:Gene Products, tat / Q000096:biosynthesis / Q000235:genetics*; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000235:genetics*; D006367:HeLa Cells / Q000382:microbiology; D006801:Humans; D007700:Kinetics; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D014158:Transcription, Genetic; D054322:tat Gene Products, Human Immunodeficiency Virus
D015696:Gene Products, tat; D012333:RNA, Messenger; D054322:tat Gene Products, Human Immunodeficiency Virus; D015500:Chloramphenicol O-Acetyltransferase