Anti-termination of transcription within the long terminal repeat of HIV-1 by tat gene product

• Published in: Nature (London) 1987-12, Vol.330 (6147), p.489-493
• Main Authors: Kao, Shaw-Yi, Calman, Andrew F, Luciw, Paul A, Peterlin, B. Matija
• Format: Article
• Language: English
• Subjects: Acetyltransferases - genetics; Acquired immune deficiency syndrome; AIDS; AIDS/HIV; Biological and medical sciences; Cell Line; Cellular biology; Chloramphenicol O-Acetyltransferase; Fundamental and applied biological sciences. Psychology; Gene Products, tat; Genes, Viral; Genetics; HIV - genetics; Human immunodeficiency virus 1; Microbiology; Nucleic Acid Hybridization; Oncogene Proteins, Viral - genetics; Plasmids; Protein Biosynthesis; Proteins; Repetitive Sequences, Nucleic Acid; RNA, Messenger - genetics; RNA, Viral - genetics; tat Gene Products, Human Immunodeficiency Virus; Transcription Factors - genetics; Transcription, Genetic; Transfection; Virology; Virus Replication
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/330489a0

Human immunodeficiency virus-1 (HIV-1) gene expression is controlled by cellular transcription factors and by virally encoded trans-activation proteins of the HIV-1 tat and art/trs genes, which are essential for viral replication. Tat trans-activates HIV-1 gene expression by interacting with the trans-acting response element (TAR) located within the HIV-1 long terminal repeat (LTR) (ref. 2). In transient expression assays, tat mediates its effects largely by increasing the steady-state levels of messenger RNA species that contain the TAR sequence at or near their 5' ends, suggesting a function for tat either in transcription or in subsequent RNA processing. The tat gene could also facilitate translation of mRNA containing the TAR sequence. To determine the mechanism of trans-activation by tat, we analysed the structure and rate of synthesis of RNA species directed by the HIV-1 LTR in transient expression assays both in the presence and absence of tat. Although the rate of HIV-1 transcription initiation was not affected by tat, transcriptional elongation beyond position +59 was seen only in the presence of tat. Thus, tat trans-activates HIV-1 transcription by relieving a specific block to transcriptional elongation within the TAR sequence.