Distinct gene expression signatures induced by viral transactivators of different HTLV-1 subgroups that confer a different risk of HAM/TSP

• 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

抄録

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.

論文

収録刊行物

• Retrovirology

  Retrovirology 15 72-, 2018-11-06

  BioMed Central

キーワード

• HTLV-1
• Virus subgroup
• HAM/TSP
• Tax
• HBZ
• Microarray

詳細情報

• CRID: 1050011251817420032
• NII論文ID: 120006847301
• ISSN: 17424690
• DOI: 10.1186/s12977-018-0454-x
• HANDLE: 20.500.12000/46016
• Web Site: https://u-ryukyu.repo.nii.ac.jp/records/2012451
• Web Site: http://link.springer.com/content/pdf/10.1186/s12977-018-0454-x.pdf
• Web Site: http://link.springer.com/article/10.1186/s12977-018-0454-x/fulltext.html
• 本文言語コード: en
• 資料種別: journal article
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