Inactivation of the HIV LTR by DNA CpG methylation: evidence for a role in latency.
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.
Bednarik
D P
DP
Johns Hopkins University, School of Medicine Oncology Center, Baltimore, MD 21205.
Cook
J A
JA
Pitha
P M
PM
D000818:Animals; D001483:Base Sequence; D015139:Blotting, Southern; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D004279:DNA, Viral / Q000037:antagonists & inhibitors / Q000235:genetics; D015226:Dinucleoside Phosphates; D015967:Gene Expression Regulation, Viral; D006678:HIV / Q000235:genetics*; D006801:Humans; D008745:Methylation; D008969:Molecular Sequence Data; D009693:Nucleic Acid Hybridization; D010957:Plasmids; D016133:Polymerase Chain Reaction; D011485:Protein Binding; D012091:Repetitive Sequences, Nucleic Acid; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection; D014709:Vero Cells
D004279:DNA, Viral; D015226:Dinucleoside Phosphates; D014157:Transcription Factors; C015772:CpG dinucleotide