Inhibition of human T cell leukaemia virus type I long terminal repeat expression by DNA methylation: implications for latency.
Human T cell leukaemia virus type I (HTLV-I) provirus DNA was found to be methylated in patients with adult T cell leukaemia. We have therefore examined the possibility that DNA methylation might contribute to HTLV-I latency. In vitro methylation of HTLV-I long terminal repeat (LTR)-chloramphenicol acetyltransferase or LTR-Luciferase constructs at eight HpaII sites, a subset of the eukaryotic methylation site CpG, resulted in a three- to fourfold inhibition of transcription in transfected cells. Inhibition of transcription by methylation of all CpG methylation sites using SssI methylase was much more pronounced (50- to 80-fold). As partial methylation of the LTR showed, methylation of the promoter region was responsible for most of the effect. Whereas cellular stimulation by a combination of phorbol 12-myristate 13-acetate and Tax was able to reverse the HpaII methylation effect, the inhibition by SssI methylation was not suppressible under these conditions. The results are in line with a possible function of DNA methylation in HTLV-I latency.
Cassens
S
S
Abteilung Virologie, Robert Koch-Institut, Berlin, Germany.
Ulrich
U
U
Beimling
P
P
Simon
D
D
D000328:Adult; D001483:Base Sequence; D015500:Chloramphenicol O-Acetyltransferase / Q000096:biosynthesis; D004279:DNA, Viral / Q000737:chemistry / Q000378:metabolism*; D015257:DNA-Cytosine Methylases / Q000378:metabolism; D016356:Gene Products, tax / Q000378:metabolism; D015368:Human T-lymphotropic virus 1 / Q000235:genetics* / Q000302:isolation & purification / Q000502:physiology; D006801:Humans; D015458:Leukemia, T-Cell / Q000821:virology; D008156:Luciferases / Q000096:biosynthesis; D008745:Methylation; D012091:Repetitive Sequences, Nucleic Acid; D015183:Restriction Mapping; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014158:Transcription, Genetic
D004279:DNA, Viral; D016356:Gene Products, tax; D008156:Luciferases; C029641:DNA modification methylase HpaII; D015257:DNA-Cytosine Methylases; D015500:Chloramphenicol O-Acetyltransferase; D013755:Tetradecanoylphorbol Acetate