タケノウチ　ノリヒロ   TAKENOUCHI NORIHIRO   竹之内　徳博    所属   関西医科大学  微生物学講座    職種   准教授
論文種別	原著(症例報告除く)
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：15537366/15537374
掲載区分	国外
巻・号・頁	13(11),pp.e1006722
著者・共著者	Furuta R, Yasunaga JI, Miura M, Sugata K, Saito A, Akari H, Ueno T, Takenouchi N, Fujisawa JI, Koh KR, Higuchi Y, Mahgoub M, Shimizu M, Matsuda F, Melamed A, Bangham CR, Matsuoka M.
発行年月	2017/11
概要	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 highthroughput 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 of HTLV-1 in vivo.
DOI	10.1371/journal.ppat.1006722
PMID	29186194