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Retrovirology. 2018 Nov 6;15(1):72. doi: 10.1186/s12977-018-0454-x.

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

Author information

1
Department of Microbiology, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama, 701-0192, Japan.
2
Laboratory of Virus Control, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto, Japan.
3
Division of Gene Regulation and Signal Transduction, Research Center for Genomic Medicine, Saitama Medical University, Saitama, Japan.
4
Department of Bioscience and Bioinformatics, Kyushu Institute of Technology, Fukuoka, Japan.
5
Department of Immunology, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.
6
Department of Social Work, Faculty of Human and Social Studies, Nagasaki International University, 2825-7 Huis Ten Bosch Machi, Sasebo, Nagasaki, 859-3298, Japan.
7
Division of Virology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
8
Department of Hematology, Rheumatology and Infectious Disease, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
9
Department of Microbiology, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama, 701-0192, Japan. mineki@med.kawasaki-m.ac.jp.

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 difference in the subgroup-specific 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 different target gene profiles; (2) the number of differentially regulated genes induced by HBZ was 2-3 times higher than that induced by Tax; (3) Tax and HBZ induced the expression of different classes of non-coding RNAs (ncRNAs); (4) the chemokine CXCL10, which has been proposed as a prognostic biomarker for HAM/TSP, was more efficiently 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 difference 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 efficiently recruited onto the promoter region of CXCL10, which contains two NF-κB binding sites, than that containing Tax-B.

CONCLUSIONS:

Our results indicate that different HTLV-1 subgroups are characterized by different patterns of host gene expression. Differential expression of pathogenesis-related genes by subgroup-specific Tax or HBZ may be associated with the onset of HAM/TSP.

KEYWORDS:

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

PMID:
30400920
PMCID:
PMC6219256
DOI:
10.1186/s12977-018-0454-x
[Indexed for MEDLINE]
Free PMC Article

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