ミウラ　ミチ   Michi Miura   三浦　未知    所属   川崎医科大学  医学部 基礎医学　微生物学    職種   助教
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Characterization of simian T-cell leukemia virus type 1 in naturally infected Japanese macaques as a model of HTLV-1 infection.
掲載誌名	正式名：Retrovirology 略　 称：Retrovirology ISSNコード：17424690/17424690
掲載区分	国外
巻・号・頁	10,pp.118
著者・共著者	Miura Michi, Yasunaga Jun-ichiro, Tanabe Junko, Sugata Kenji, Zhao Tiejun, Ma Guangyong, Miyazato Paola, Ohshima Koichi, Kaneko Akihisa, Watanabe Akino, Saito Akatsuki, Akari Hirofumi, Matsuoka Masao
担当区分	筆頭著者
発行年月	2013/10
概要	BACKGROUND:Human T-cell leukemia virus type 1 (HTLV-1) causes chronic infection leading to development of adult T-cell leukemia (ATL) and inflammatory diseases. Non-human primates infected with simian T-cell leukemia virus type 1 (STLV-1) are considered to constitute a suitable animal model for HTLV-1 research. However, the function of the regulatory and accessory genes of STLV-1 has not been analyzed in detail. In this study, STLV-1 in naturally infected Japanese macaques was analyzed.RESULTS:We identified spliced transcripts of STLV-1 corresponding to HTLV-1 tax and HTLV-1 bZIP factor (HBZ). STLV-1 Tax activated the NFAT, AP-1 and NF-κB signaling pathways, whereas STLV-1 bZIP factor (SBZ) suppressed them. Conversely, SBZ enhanced TGF-β signaling and induced Foxp3 expression. Furthermore, STLV-1 Tax activated the canonical Wnt pathway while SBZ suppressed it. STLV-1 Tax enhanced the viral promoter activity while SBZ suppressed its activation. Then we addressed the clonal proliferation of STLV-1⁺ cells by massively sequencing the provirus integration sites. Some clones proliferated distinctively in monkeys with higher STLV-1 proviral loads. Notably, one of the monkeys surveyed in this study developed T-cell lymphoma in the brain; STLV-1 provirus was integrated in the lymphoma cell genome. When anti-CCR4 antibody, mogamulizumab, was administered into STLV-1-infected monkeys, the proviral load decreased dramatically within 2 weeks. We observed that some abundant clones recovered after discontinuation of mogamulizumab administration.CONCLUSIONS:STLV-1 Tax and SBZ have functions similar to those of their counterparts in HTLV-1. This study demonstrates that Japanese macaques naturally infected with STLV-1 resemble HTLV-1 carriers and are a suitable model for the investigation of persistent HTLV-1 infection and asymptomatic HTLV-1 carrier state.
DOI	10.1186/1742-4690-10-118
PMID	24156738