Fig. 7. Model for latency reversal and cell death induced by DDX3 inhibition.

DDX3 inhibition results in HIV-1 latency reversal, possibly via NF-κB activation, and BIRC5 and HSPA1B downregulation in both uninfected bystander and latent proviral-containing cells. The HIV-1 provirus is reactivated generating vRNA that can activate innate antiviral signalling pathways, phosphorylate IRF3 and induce IFNβ expression, which when combined with BIRC5 or HSPA1B downregulation, results in upregulated Bax, downregulated BCl2, increased cleaved caspase-3 and apoptosis of the vRNA-expressing cells, but leaving the uninfected cells unharmed, thereby resulting in a reduction in the viral reservoir.