NF-κB-Driven HIV-1 Gene Expression in Human Cells Is Independent of Poly(ADP-ribose) polymerase-1 Function.

The cellular enzyme poly (ADP-ribose) polymerase-1 (PARP-1) is required for NF-κB to activate inflammatory and immune response gene expression. NF-κB is also an important transcription factor in HIV-1 gene expression during active replication and latency reactivation. Therefore, enhancing NF-κB signaling is an alternative for HIV-1 latency reactivation, but significant systemic side effects related to the NF-κB role in inflammatory and immune responses are predictable. To verify this prediction, we determined whether PARP-1 is required in NF-κB-dependent HIV-1 gene expression in a human CD4+ T lymphoblastoid cell line (SUP-T1) and HEK 293T cells. Our findings indicated that PARP-1 knockout does not impair HIV-1 infection or gene expression. Specifically, NF-κB-dependent HIV-1 gene expression was not impaired by PARP-1 deficiency, highlighting an important transcriptional regulatory difference between HIV-1 and inflammatory and immune activation genes. Our findings define a negligible role of PARP-1 in HIV-1 gene expression, suggesting that PARP-1 antagonism could ameliorate the expected inflammatory response with latency-reactivating agents that act through the NF-κB signaling pathway.