ART suppresses HIV but cannot cure it due to latent infected cells. Latency is maintained by blocks to HIV transcription, including initiation, elongation, and especially post-transcriptional steps like splicing. Current latency-reversing agents (LRAs) have failed to reduce the HIV reservoir, likely because they don't target these later blocks.
The PI developed RT-ddPCR assays revealing that latency in ART-suppressed individuals is mainly due to reversible blocks to elongation, completion, and splicing. A primary cell model confirmed that splicing blocks are key to latency. RNA-seq identified host genes linked to splicing, suggesting new therapeutic targets.
The VIRNA project aims to identify cellular factors regulating post-transcriptional blocks and discover compounds to modulate them, an unmet need in HIV therapy. This work will lay the groundwork for future trials targeting HIV latency.
