Figure 6.
MK-2048 reduces PVLs and induces ER stress–related apoptosis specifically in HTLV-1–infected cells in HTLV-1–carrier PBMCs. (A-B) PBMCs obtained from 4 asymptomatic carriers (numbers 1 to 4) were incubated for 4 days with the indicated concentrations of MK-2048. (A) PVL (copies per 100 cells) in each culture was measured using quantitative PCR. The bar graph shows the mean (carriers numbers 1 to 4) ratio of PVL of MK-2048–treated cells relative to that of MK-2048–untreated cells. (B) Simultaneously counted cell numbers. The bar graph shows the mean (carriers numbers 1 to 4) ratio of MK-2048–treated cell numbers relative to MK-2048–untreated cell numbers. (C) Representative immunostaining for CD4 (pink), CADM1 (red), and CHOP (green) in carrier PBMCs following 25 μM MK-2048 treatment. HTLV-1–infected cells (CD4+, CADM1+) are shown as yellow squares. Bars represent 20 μm. (D-E) PBMCs obtained from 6 asymptomatic carriers (n = 6; average PVL = 4.54 ± 2.82) were incubated for 16 hours with 25 μM MK-2048. (D) Representative FACS profiles of CADM1 and CD4 in DAPI− CD14− cells (left) and the expression of annexin V in the DAPI− CD14−CD4+ cell fraction (right) of HTLV-1–carrier PBMCs 16 hours after 25 μM MK2048 treatment. Data are expressed as the mean ± SD. (E) Box plots showing the percentage of annexin V+ apoptotic cells in DAPI− CD14−CD4+ cells of HTLV-1–carrier PBMCs 16 hours following treatment with 25 μM MK2048. DMSO, dimethyl sulfoxide.