CNS-specific regulatory elements in brain-derived HIV-1 strains affect responses to latency-reversing agents with implications for cure strategies

摘要: Latency-reversing agents (LRAs), including histone deacetylase inhibitors (HDACi), are being investigated as a strategy to eliminate latency in HIV-infected patients on suppressive antiretroviral therapy. The effectiveness of LRAs activating latent infection HIV strains derived from the central nervous system (CNS) is unknown. Here we show that CNS-derived HIV-1 possess polymorphisms within and surrounding Sp transcription factor motifs long terminal repeat (LTR). These result decreased ability specificity protein 1 bind LTRs, reducing transcriptional activity viruses. mutations viruses less responsive activation by HDACi panobinostat romidepsin compared with lymphoid-derived same subjects. Our findings suggest residing CNS have unique regulatory mechanisms, which impact regulation latency, consideration essential for development eradication strategies.