Constitutive expression of interferon regulatory factor, IRF5 in HTLV-1-infected T cells.

2014 Fiscal Year Final Research Report

• Project/Area Number: 25830085
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Tumor biology
• Research Institution: University of the Ryukyus
• Principal Investigator: ISHIKAWA Chie 琉球大学, 亜熱帯島嶼科学超域研究推進機構, 助教 (90542358)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: 成人T細胞白血病・リンパ腫（ATLL） / HTLV-1 / インターフェロン（IFN）調節因子(IRF)5 / Tax / TNF-α

Outline of Final Research Achievements

We examined the mechanisms underlying the expression and regulation of IRF5 in HTLV-1-infected T-cells. IRF5 was constitutively transcribed into three distinct alternatively spliced isoforms (V1, V3 and V4) in HTLV- 1-infected T-cell lines but not in uninfected T-cell lines. IRF5 protein was located in the nuclei of HTLV-1-infected T-cell lines and ATLL cells present in lymph nodes and skin lesions. IRF5 mRNA expression was induced following infection of T cells with HTLV-1, and specifically by viral oncoprotein Tax. Tax also activated IRF5-V3 promoter. Microarray analysis of IRF5-expressing uninfected T cells demonstrated that IRF5 induced the expression of TNF family cytokines but not the expression of IFN. Especially, TNF-α expression was correlated with infection of HTLV-1, and expression of Tax and IRF5 in T-cell lines. Tax also induced TNF-α expression. The results suggest that IRF5 is a Tax-regulated gene, and its expression may be associated with the pathogenesis of ATLL.

Free Research Field

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