NF-kappa B/Rel: agonist and antagonist roles in HIV-1 latency

作者：Chan Jonathan K L; Greene Warner C^*

来源：Current Opinion in HIV and AIDS, 2011, 6(1): 12-18.

DOI：10.1097/COH.0b013e32834124fd

• drug-free remission
• HIV-1 latency
• homeostatic proliferation
• NF-kappa B
• viral eradication

Purpose of review
To discuss recent advances in our understanding of the diverse roles of NF-kappa B/Rel family members in HIV-1 latency.
Recent findings
Various NF-kappa B/Rel family members can reinforce maintenance of HIV-1 latency. For example, p50 recruits histone deacetylase 1 to the HIV-1 long terminal repeat promoting chromatin condensation and reduced RNA Pol II recruitment. Low-level NF-kappa B activation during homeostatic proliferation of memory CD4 T cells induced by IL-7 and TCR signaling or OX40 action promotes expression of antiapoptotic gene targets such as BCL2 and BCLXL. Additionally, the I kappa B kinase phosphorylates FOXO3a transcription factor, blocking its induction of proapoptotic genes. These combined effects promote memory CD4 T-cell survival, thus maintaining the latent reservoir. Conversely, when the nontumorigenic phorbol ester prostratin is combined with histone deacetylase inhibitors, potent synergistic activation of latent HIV-1 occurs involving nuclear expression of NF-kappa B.
Summary
These recent findings highlight both the antagonistic and agonistic effects of the NF-kappa B signaling pathway on HIV-1 latency. Synergistic inducers might be useful for flushing of latent virus from reservoirs in infected patients. The ultimate, albeit lofty, goal is to achieve full viral eradication. However, a more reasonable goal might be a functional cure where patients experience a drug-free remission.

• 出版日期2011-1