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Title :Distinct gene expression signatures induced by viral transactivators of different HTLV-1 subgroups that confer a different risk of HAM/TSP
Authors :Naito, Tadasuke
Yasunaga, Jun-ichirou
Mitobe, Yuichi
Shirai, Kazumasa
Sejima, Hiroe
Ushirogawa, Hiroshi
Tanaka, Yuetsu
Nakamura, Tatsufumi
Hanada, Kousuke
Fujii, Masahiro
Matsuoka, Masao
Saito, Mineki
Issue Date :6-Nov-2018
Abstract :Background: Among human T cell leukemia virus type 1 (HTLV-1)-infected individuals, there is an association between HTLV-1 tax subgroups (subgroup-A or subgroup-B) and the risk of HAM/TSP in the Japanese population. To investigate the role of HTLV-1 subgroups in viral pathogenesis, we studied the functional diference in the subgroupspecifc viral transcriptional regulators Tax and HBZ using microarray analysis, reporter gene assays, and evaluation of viral-host protein–protein interaction. Results: (1) Transcriptional changes in Jurkat Tet-On human T-cells that express each subgroup of Tax or HBZ protein under the control of an inducible promoter revealed diferent target gene profles; (2) the number of diferentially regulated genes induced by HBZ was 2–3 times higher than that induced by Tax; (3) Tax and HBZ induced the expres‑ sion of diferent classes of non-coding RNAs (ncRNAs); (4) the chemokine CXCL10, which has been proposed as a prognostic biomarker for HAM/TSP, was more efciently induced by subgroup-A Tax (Tax-A) than subgroup-B Tax (Tax-B), in vitro as well as in unmanipulated (ex vivo) PBMCs obtained from HAM/TSP patients; (5) reporter gene assays indicated that although transient Tax expression in an HTLV-1-negative human T-cell line activated the CXCL10 gene promoter through the NF-κB pathway, there was no diference in the ability of each subgroup of Tax to activate the CXCL10 promoter; however, (6) chromatin immunoprecipitation assays showed that the ternary complex containing Tax-A is more efciently recruited onto the promoter region of CXCL10, which contains two NF-κB binding sites, than that containing Tax-B. Conclusions: Our results indicate that diferent HTLV-1 subgroups are characterized by diferent patterns of host gene expression. Diferential expression of pathogenesis-related genes by subgroup-specifc Tax or HBZ may be asso‑ ciated with the onset of HAM/TSP.
URL :https://doi.org/10.1186/s12977-018-0454-x
Type Local :雑誌掲載論文
ISSN :1742-4690
Publisher :BioMed Central
URI :http://hdl.handle.net/20.500.12000/46016
Citation :Retrovirology Vol.15
Appears in Collections:Peer-reviewed Journal Articles (Faculty of Medicine)

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