2013 Fiscal Year Final Research Report
Study of retrovirus latency and its heterogeneity
| Project/Area Number |
24790436
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Virology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
YAMAGISHI Makoto 東京大学, 新領域創成科学研究科, 特任研究員 (90625261)
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| Project Period (FY) |
2012-04-01 – 2014-03-31
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| Keywords | エピジェネティクス / HIV-1 / HTLV-1 / 潜伏化 / ATL |
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| Research Abstract |
The HIV-1 latency remains a principal obstacle in curing AIDS. We revealed a molecular characterization of distinct populations at an early phase of HIV-1 infection. We developed an original dual-color reporter virus to monitor LTR kinetics from establishment to maintenance stage. We found that there are two ways of latency establishment i.e., by immediate silencing and slow inactivation from active infection. Histone covalent modifications, particularly PRC2-mediated H3K27 trimethylation, appeared to dominate viral transcription at the early phase. PRC2 also contributes to time-dependent LTR dormancy.
To view epigenetic landscape in ATL and HTLV-1-infected cells, we performed global histone methylation profiling by high-resolution promoter array. We successfully detected the numerous gene promoters with aberrant repressive H3K27me3 mark in ATL cells. Interestingly, Tax-triggered immortalizing cells partially mimicked the methylation pattern observed in ATL cells.
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[Journal Article] CADM1 expression and stepwise downregulation of CD7 are closely associated with clonal expansion of HTLV-1-infected cells in adult T-cell leukemia/lymphoma2014
Author(s)
Kobayashi S, Nakano K, Watanabe E, Ishigaki T, Ohno N, Yuji K, Oyaizu N, Asanuma S, Yamagishi M, Yamochi T, Watanabe N, Tojo A, Watanabe T, Uchimaru K.
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Journal Title
Clin Cancer Res
Volume: (in press)
Peer Reviewed
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[Journal Article] Adult T-cell leukemia cells are characterized by abnormalities of Helios expression that promotes T-cell growth2013
Author(s)
Asanuma S, Yamagishi M, Kawanami K, Nakano K, Sato-Otsubo A, Muto S, Sanada M, Yamochi T, Kobayashi S, Utsunomiya A, Iwanaga M, Yamaguchi K, Uchimaru K, Ogawa S, Watanabe T.
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Journal Title
Cancer Sci
Volume: 104(8)
Pages: 1097-1106
DOI
Peer Reviewed
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[Journal Article] Viral interference with host mRNA surveillance, the nonsense-mediated mRNA decay (NMD) pathway, through a new function of HTLV-1 Rex : implications for retroviral replication2013
Author(s)
Nakano K, Ando T, Yamagishi M, Yokoyama K, Ishida T, Ohsugi T, Tanaka Y, Brighty DW, Watanabe T.
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Journal Title
Microbes Infect
Volume: 15(6-7)
Pages: 491-505
Peer Reviewed
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[Journal Article] Polycomb-mediated loss of miR-31 activates NIK-dependent NF-kB pathway in adult T-cell leukemia and other cancers2012
Author(s)
Yamagishi M, Nakano K, Miyake A, Yamochi T, Kagami Y, Tsutsumi A, Matsuda Y, Sato-Otsubo A, Muto S, Utsunomiya A, Yamaguchi K, Uchimaru K, Ogawa S, Watanabe T.
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Journal Title
Cancer Cell
Volume: 21(1)
Pages: 121-135
DOI
Peer Reviewed
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[Presentation] Molecular hallmarks of adult T cell leukemia : miRNA, pigenetics, and emerging signaling abnormalities2013
Author(s)
Yamagishi M, Fujikawa D, Kurokawa N, Soejima A, Takahashi R, Sakai N, Nakagawa S, Nakano K, Kobayashi S, Utsunomiya A, Yamaguchi K, Uchimaru K, Ogawa S, Watanabe T
Organizer
16^<th> International Conference on Human Retrovirology HTLV and Related Viruses
Place of Presentation
Montreal, Canada(Oral)
Year and Date
20130626-30
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