Journal of NeuroVirology

, Volume 22, Issue 4, pp 416–430 | Cite as

HTLV-1 subgroups associated with the risk of HAM/TSP are related to viral and host gene expression in peripheral blood mononuclear cells, independent of the transactivation functions of the viral factors

  • Keiko Yasuma
  • Toshio Matsuzaki
  • Yoshihisa Yamano
  • Hiroshi Takashima
  • Masao Matsuoka
  • Mineki Saito
Article
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Abstract

Among human T cell leukemia virus type 1 (HTLV-1)-infected individuals, the risk of developing HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) across lifetime differs between ethnic groups. There is an association between HTLV-1 tax gene subgroups (subgroup-A or subgroup-B) and the risk of HAM/TSP in the Japanese population. In this study, we investigated the full-length proviral genome sequences of various HTLV-1-infected cell lines and patient samples. The functional differences in the viral transcriptional regulators Tax and HTLV-1 bZIP factor (HBZ) between each subgroup and the relationships between subgroups and the clinical and laboratory characteristics of HAM/TSP patients were evaluated. The results of these analyses indicated the following: (1) distinct nucleotide substitutions corresponding to each subgroup were associated with nucleotide substitutions in viral structural, regulatory, and accessory genes; (2) the HBZ messenger RNA (mRNA) expression in HTLV-1-infected cells was significantly higher in HAM/TSP patients with subgroup-B than in those with subgroup-A; (3) a positive correlation was observed between the expression of HBZ mRNA and its target Foxp3 mRNA in HAM/TSP patients with subgroup-B, but not in patients with subgroup-A; (4) no clear differences were noted in clinical and laboratory characteristics between HAM/TSP patients with subgroup-A and subgroup-B; and (5) no functional differences were observed in Tax and HBZ between each subgroup based on reporter gene assays. Our results indicate that although different HTLV-1 subgroups are characterized by different patterns of viral and host gene expression in HAM/TSP patients via independent mechanisms of direct transcriptional regulation, these differences do not significantly affect the clinical and laboratory characteristics of HAM/TSP patients.

Keywords

HTLV-1 Virus subgroup HAM/TSP Tax HBZ Foxp3 
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Notes

Acknowledgments

This work was supported by KAKENHI from the Japan Society for the Promotion of Science (JSPS) (Grant Numbers 21590512, 24590556, and 15K09345); the Health and Labor Sciences Research Grants (research on rare and intractable diseases, Grant Numbers H22-013, H23-126, H25-023, and H25-028); the Japan Agency for Medical Research and Development (AMED); the Project of Establishing Medical Research Base Networks Against Infectious Diseases in Okinawa; the Novartis Foundation for the Promotion of Science (Japan); and the Joint Usage/Research Center Program of the Institute for Virus Research, Kyoto University.

Compliance with ethical standards

The Institutional Review Boards of the authors’ institutions approved this research and written informed consent was obtained from all study participants.

Conflict of interest

The authors declare that they have no competing interests.

Supplementary material

13365_2015_407_MOESM1_ESM.pptx (179 kb)
Supplementary Figure 1 Subgroup specific tax nucleotide substitutions are linked with those of viral structural, regulatory, and accessory HTLV-1 genes. Nucleotide substitutions of tax subgroups (subgroup-A or subgroup-B) are linked with nucleotide substitutions of LTR, p12, p30, envelope (env), the gal/pol precursor, and HBZ HTLV-1 genes. A. Nucleotide substitutions in the viral long terminal repeat (LTR). B. Amino acid substitution in the HTLV-1 accessory protein p12. C. Amino acid substitutions in the HTLV-1 accessory protein p30. D. Amino acid substitutions in the HTLV-1 structural protein Env. E. Amino acid substitution in the gag/pol precursor. F. Amino acid substitution in the HBZ. (PPTX 179 kb)
13365_2015_407_MOESM2_ESM.docx (17 kb)
Supplementary Table 1 Osame Motor Disability Score (OMDS) for evaluation of motor dysfunction in HAM/TSP patents. (DOCX 16 kb)

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Copyright information

© Journal of NeuroVirology, Inc. 2015

Authors and Affiliations

  • Keiko Yasuma
    • 1
  • Toshio Matsuzaki
    • 2
  • Yoshihisa Yamano
    • 3
  • Hiroshi Takashima
    • 2
  • Masao Matsuoka
    • 1
  • Mineki Saito
    • 4
  1. 1.Laboratory of Virus Control, Institute for Virus ResearchKyoto UniversityKyotoJapan
  2. 2.Department of Neurology and GeriatricsKagoshima University Graduate School of Medical and Dental SciencesKagoshimaJapan
  3. 3.Department of Rare Diseases Research, Institute of Medical ScienceSt. Marianna University School of MedicineKanagawaJapan
  4. 4.Department of MicrobiologyKawasaki Medical SchoolKurashikiJapan

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