Inactivation of the HIV LTR by DNA CpG methylation: evidence for a role in latency

• Published in: The EMBO journal Vol. 9; no. 4; pp. 1157 - 1164
• Main Authors: Bednarik, D.P., Cook, J.A., Pitha, P.M.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group 01-04-1990
• Subjects: Animals; Base Sequence; Biological and medical sciences; Blotting, Southern; Cell Line; Cell Nucleus - metabolism; Dinucleoside Phosphates; DNA, Viral - antagonists & inhibitors; DNA, Viral - genetics; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation, Viral; Genetics; HIV - genetics; Humans; Methylation; Microbiology; Molecular Sequence Data; Nucleic Acid Hybridization; Plasmids; Polymerase Chain Reaction; Protein Binding; Repetitive Sequences, Nucleic Acid; Transcription Factors - metabolism; Transcription, Genetic; Transfection; Vero Cells; Virology; Transcription; Retroviridae; Molecular interaction; Gel retardation technique; Inactivation; Latency; Infection; Virus; Site specificity; Polymerase chain reaction; Transfection; Reporter gene; DNA; Viral disease; Trans acting regulatory factor; Inhibition; LTR sequence; Human immunodeficiency virus; Mechanism of action; Southern blotting; Methylation; Enzymatic reaction
• ISSN: 0261-4189; 1460-2075
• DOI: 10.1002/j.1460-2075.1990.tb08222.x

Infection of cells by HIV can result in a period of quiescence or latency which may be obviated by treatment with inducing agents such as 5‐azacytidine. Evidence from these experiments demonstrate the existence of two CpG sites in the HIV LTR which can silence transcription of both reporter genes (CAT) and infectious proviral DNA when enzymatically methylated. This transcriptional block was consistently overcome by the presence of the trans‐activator tat without significant demethylation of the HIV LTR. These results suggest that DNA hypermethylation of the HIV LTR may change the binding characteristics between LTR sequences and cellular proteins, thereby suppressing HIV LTR transcription and modulating viral expression.