Fig. 3: Virological and immunological significance of the OCR function in HTLV-1 infection.
From: Intragenic viral silencer element regulates HTLV-1 latency via RUNX complex recruitment
a, The nucleotide and protein sequences of silent mutations (s-mut) in the RUNX binding site (underlined) within the OCR. Mutated nucleotides are shown in red. Luciferase reporter assays were performed using Jurkat T cells 48 h after transfection. b, Experimental workflow illustrating the establishment of reporter cells (JET cells) infected with wt- or s-mut-HTLV-1. c, Signals from RUNX1, CBFβ or HDAC3 ChIP-seq in the HTLV-1 provirus for wt- and s-mut-HTLV-1-infected JET cells. d, Representative RT-qPCR results showing tax or hbz mRNA expression levels in JET cells infected with wt- or s-mut-HTLV-1. e, Supernatant p19 ELISA results from JET cells infected with wt- or s-mut-HTLV-1 with or without PMA–ionomycin stimulation. f, PVLs during long-term culture in wt- or s-mut-HTLV-1-infected JET cells after tdTomato sorting. The data presented are representative of two independent experiments. g, Tax expression after treatment with RUNX1 inhibitor (Ro5-3335). Tax expression was analysed by expression of the reporter protein tdTomato. h, Effect of RUNX1 inhibitor on ex vivo Tax expression using PBMCs of ACs and patients with ATL. Tax-expressing CD4+ T cells were measured by flow cytometry. i, IFNγ ELISPOT assay results from Tax TCR-transduced CD8+ T cells cocultured with wt- or s-mut-HTLV-1-infected JET cells expressing HLA-A*24:02 (A24). At least two independent experiments were performed. The bars and error bars represent the mean ± s.d. of results in triplicate experiments. P values were calculated using a two-sided, unpaired Student’s t-test (n.d., not detectable).
