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

Chan, Jonathan KL; Greene, Warner C

Current Opinion in HIV and AIDS: January 2011 - Volume 6 - Issue 1 - p 12–18
doi: 10.1097/COH.0b013e32834124fd
HIV reservoirs: from pathogenesis to drug development: Edited by Robert F. Siliciano and Janet D. Siliciano

Purpose of review To discuss recent advances in our understanding of the diverse roles of NF-κB/Rel family members in HIV-1 latency.

Recent findings Various NF-κB/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-κB 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 IκB 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-κB.

Summary These recent findings highlight both the antagonistic and agonistic effects of the NF-κB 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.

Gladstone Institute of Virology and Immunology, Departments of Medicine and Microbiology and Immunology, University of California, San Francisco, California, USA

Correspondence to Warner C. Greene, MD, PhD, Gladstone Institute of Virology and Immunology, 1650 Owens Street, San Francisco, CA 94158, USA Tel: +1 415 734 4805; e-mail: wgreene@gladstone.ucsf.edu

© 2011 Lippincott Williams & Wilkins, Inc.