Investigation on molecular mechanisms of HAM/TSP pathogenesis mediated by the interactions between HBZ and its target host factors.

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K09345
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurology
• Research Institution: Kawasaki Medical School
• Principal Investigator: Saito Mineki 川崎医科大学, 医学部, 教授 (40398285)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: HTLV-1 / HBZ / 慢性炎症 / 免疫老化

Outline of Final Research Achievements

Among HTLV-1-infected individuals, there is an association between HTLV-1 subgroups (subgroup-A or -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 regulator HBZ by microarray analysis followed by validation using clinical samples derived from HTLV-1 infected individuals. Transcriptional changes in Jurkat Tet-On human T-cells that express each subgroup of HBZ protein under the control of an inducible promoter showed different target gene profiles. Interestingly, HBZ induced the expression of different classes of non-coding RNAs (ncRNAs), as well as genes related to inflammation and CD4 T-cell senescence. These newly identified HBZ target genes may constitute candidates for novel biomarker and therapeutic target of HAM/TSP.

Free Research Field

ウイルス学・神経内科学