Document Detail

Silencing of human T-cell leukemia virus type I gene transcription by epigenetic mechanisms.
MedLine Citation:
PMID:  16242045     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Human T-cell leukemia virus type I (HTLV-I) causes adult T-cell leukemia (ATL) after a long latent period. Among accessory genes encoded by HTLV-I, the tax gene is thought to play a central role in oncogenesis. However, Tax expression is disrupted by several mechanims including genetic changes of the tax gene, deletion/hypermethylation of 5'-LTR. To clarify the role of epigenetic changes, we analyzed DNA methylation and histone modification in the whole HTLV-I provirus genome. RESULTS: The gag, pol and env genes of HTLV-I provirus were more methylated than pX region, whereas methylation of 5'-LTR was variable and 3'-LTR was not methylated at all. In ATL cell lines, complete DNA methylation of 5'-LTR was associated with transcriptional silencing of viral genes. HTLV-I provirus was more methylated in primary ATL cells than in carrier state, indicating the association with disease progression. In seroconvertors, DNA methylation was already observed in internal sequences of provirus just after seroconversion. Taken together, it is speculated that DNA methylation first occurs in the gag, pol and env regions and then extends in the 5' and 3' directions in vivo, and when 5'-LTR becomes methylated, viral transcription is silenced. Analysis of histone modification in the HTLV-I provirus showed that the methylated provirus was associated with hypoacetylation. However, the tax gene transcript could not be detected in fresh ATL cells regardless of hyperacetylated histone H3 in 5'-LTR. The transcription rapidly recovered after in vitro culture in such ATL cells. CONCLUSION: These results showed that epigenetic changes of provirus facilitated ATL cells to evade host immune system by suppressing viral gene transcription. In addition, this study shows the presence of another reversible mechanism that suppresses the tax gene transcription without DNA methylation and hypoacetylated histone.
Yuko Taniguchi; Kisato Nosaka; Jun-ichirou Yasunaga; Michiyuki Maeda; Nancy Mueller; Akihiko Okayama; Masao Matsuoka
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Publication Detail:
Type:  Journal Article     Date:  2005-10-22
Journal Detail:
Title:  Retrovirology     Volume:  2     ISSN:  1742-4690     ISO Abbreviation:  Retrovirology     Publication Date:  2005  
Date Detail:
Created Date:  2005-11-24     Completed Date:  2006-07-26     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  101216893     Medline TA:  Retrovirology     Country:  England    
Other Details:
Languages:  eng     Pagination:  64     Citation Subset:  IM    
Laboratory of Virus Immunology, Institute for Virus Research, Kyoto University, Kyoto 606-8507, Japan.
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MeSH Terms
Carrier State / virology
Cell Line
DNA Methylation
Epigenesis, Genetic*
Gene Silencing*
Histones / metabolism
Human T-lymphotropic virus 1 / genetics*
Leukemia-Lymphoma, Adult T-Cell / virology
Proviruses / genetics
Terminal Repeat Sequences
Transcription, Genetic*
Reg. No./Substance:

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