Figure 5
Activity of LRAs to induce viral transcription of CNS- and lymphoid-derived LTRs in CNS cells. CNS cells were transfected with LTR luciferase constructs containing LTRs from the CNS and lymphoid compartments of patients and subjected to HIV-1 transcription assays either in the presence or absence of LRAs and/or Tat. Treatments included Panobinostat (a), Romidepsin (b), Vorinostat (c), Chaetocin (d), Disulfiram (e), JQ1 (f), Tat (g) and JQ1 + Tat (h). Lymphoid isolates are in red, CNS isolates in blue. The activity of the LRAs was plotted as fold change over basal activity for each construct with results made relative to Z1 (set as 1, with Z1 fold change values quoted in each panel). Control promoters (shown in black and gray) based on consensus T-cell isolate HXB2 are indicated by Z (Z1: wild-type sequence; Z1(TAR-): deletion of TAR region; Z5: mutation of SpI; Z6: mutation of SpII and III; Z7:mutation of SpIII and NF-κB). Patient isolates are indicated. Data shown are representative of four independent experiments, each experiment performed in triplicate. Shown are the means and s.e.m. of these data. Significance values (calculated using student's t-test): *P=<0.05, **P=<0.01, ***P=<0.001, ns=not significant. Black values indicate significance of isolates relative to Z1 T-cell-derived consensus sequence (HXB2), red values represent significance of CNS-derived isolates relative to lymphoid-derived isolates from the same patient. CNS, central nervous system; LRA, latency-reversing agent; LTR, long terminal repeat.
