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	Kinetics of HTLV-1 reactivation from latency quantified by single-molecule RNA FISH and stochastic modelling.
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	15(11),pp.e1008164
著者・共著者	Miura Michi, Dey Supravat, Ramanayake Saumya, Singh Abhyudai, Rueda David S, Bangham Charles R M
担当区分	筆頭著者
発行年月	2019/11
概要	The human T cell leukemia virus HTLV-1 establishes a persistent infection in vivo in which the viral sense-strand transcription is usually silent at a given time in each cell. However, cellular stress responses trigger the reactivation of HTLV-1, enabling the virus to transmit to a new host cell. Using single-molecule RNA FISH, we measured the kinetics of the HTLV-1 transcriptional reactivation in peripheral blood mononuclear cells (PBMCs) isolated from HTLV-1+ individuals. The abundance of the HTLV-1 sense and antisense transcripts was quantified hourly during incubation of the HTLV-1-infected PBMCs ex vivo. We found that, in each cell, the sense-strand transcription occurs in two distinct phases: the initial low-rate transcription is followed by a phase of rapid transcription. The onset of transcription peaked between 1 and 3 hours after the start of in vitro incubation. The variance in the transcription intensity was similar in polyclonal HTLV-1+ PBMCs (with tens of thousands of distinct provirus insertion sites), and in samples with a single dominant HTLV-1+ clone. A stochastic simulation model was developed to estimate the parameters of HTLV-1 proviral transcription kinetics. In PBMCs from a leukemic subject with one dominant T-cell clone, the model indicated that the average duration of HTLV-1 sense-strand activation by Tax (i.e. the rapid transcription) was less than one hour. HTLV-1 antisense transcription was stable during reactivation of the sense-strand. The antisense transcript HBZ was produced at an average rate of ~0.1 molecules per hour per HTLV-1+ cell; however, between 20% and 70% of HTLV-1-infected cells were HBZ-negative at a given time, the percentage depending on the individual subject. HTLV-1-infected cells are exposed to a range of stresses when they are drawn from the host, which initiate the viral reactivation. We conclude that whereas antisense-strand transcription is stable throughout the stress response, the HTLV-1 sense-strand reactivati
DOI	10.1371/journal.ppat.1008164
PMID	31738810