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	Human T-cell leukemia virus type 1 infects multiple lineage hematopoietic cells in vivo.
掲載誌名	正式名：PLOS Pathogens 略　 称：PLoS Pathog ISSNコード：15537374/15537366
掲載区分	国外
巻・号・頁	13(11),pp.e1006722
著者・共著者	Furuta Rie, Yasunaga Jun-Ichirou, Miura Michi, Sugata Kenji, Saito Akatsuki, Akari Hirofumi, Ueno Takaharu, Takenouchi Norihiro, Fujisawa Jun-Ichi, Koh Ki-Ryang, Higuchi Yusuke, Mahgoub Mohamed, Shimizu Masakazu, Matsuda Fumihiko, Melamed Anat, Bangham Charles R, Matsuoka Masao
発行年月	2017/11
概要	Human T-cell leukemia virus type 1 (HTLV-1) infects mainly CD4+CCR4+ effector/memory T cells in vivo. However, it remains unknown whether HTLV-1 preferentially infects these T cells or this virus converts infected precursor cells to specialized T cells. Expression of viral genes in vivo is critical to study viral replication and proliferation of infected cells. Therefore, we first analyzed viral gene expression in non-human primates naturally infected with simian T-cell leukemia virus type 1 (STLV-1), whose virological attributes closely resemble those of HTLV-1. Although the tax transcript was detected only in certain tissues, Tax expression was much higher in the bone marrow, indicating the possibility of de novo infection. Furthermore, Tax expression of non-T cells was suspected in bone marrow. These data suggest that HTLV-1 infects hematopoietic cells in the bone marrow. To explore the possibility that HTLV-1 infects hematopoietic stem cells (HSCs), we analyzed integration sites of HTLV-1 provirus in various lineages of hematopoietic cells in patients with HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) and a HTLV-1 carrier using the high-throughput sequencing method. Identical integration sites were detected in neutrophils, monocytes, B cells, CD8+ T cells and CD4+ T cells, indicating that HTLV-1 infects HSCs in vivo. We also detected Tax protein in myeloperoxidase positive neutrophils. Furthermore, dendritic cells differentiated from HTLV-1 infected monocytes caused de novo infection to T cells, indicating that infected monocytes are implicated in viral spreading in vivo. Certain integration sites were re-detected in neutrophils from HAM/TSP patients at different time points, indicating that infected HSCs persist and differentiate in vivo. This study demonstrates that HTLV-1 infects HSCs, and infected stem cells differentiate into diverse cell lineages. These data indicate that infection of HSCs can contribute to the persistence and spread
DOI	10.1371/journal.ppat.1006722
PMID	29186194