NF-κB/Rel: agonist and antagonist roles in HIV-1 latency.
NF-κB/Rel: agonist and antagonist roles in HIV-1 latency.
复制标题
DOI：
10.1097/coh.0b013e32834124fd
复制
发表时间：
2011-01
影响因子：
4.1
通讯作者：
Greene WC
中科院分区：
文献类型：
--
作者：
Chan JK;Greene WC
探讨NF-κB/Rel家族成员在HIV-1潜伏期中不同作用的最新进展。不同的NF-κB/Rel家族成员可以加强HIV-1潜伏期的维持。例如，p50将组蛋白脱乙酰基酶1募集到HIV-1长末端重复序列，促进染色质浓缩和减少RNA Pol II募集。在由IL-7和TCR信号传导或OX 40作用诱导的记忆性CD 4 T细胞稳态增殖期间，低水平NF-κB活化促进抗凋亡基因靶标如BCL 2和BCL XL的表达。此外，IκB激酶磷酸化FOXO 3 a转录因子，阻断其诱导促凋亡基因。这些组合效应促进记忆性CD 4 T细胞存活，从而维持潜在的储存库。相反，当非致瘤性佛波醇酯prostratin与组蛋白去乙酰化酶抑制剂联合使用时，潜在的HIV-1的有效协同激活发生，涉及NF-κB的核表达。这些最新的发现强调了NF-κB信号通路对HIV-1潜伏期的拮抗和激动作用。协同诱导剂的作用可能是有用的冲洗潜伏病毒从水库感染的病人。最终的目标虽然崇高，但却是实现完全根除病毒。然而，一个更合理的目标可能是功能性治愈，其中患者经历无药物缓解。
To discuss recent advances in our understanding of the diverse roles of NF-κB/Rel family members in HIV-1 latency. 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 like 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. These recent findings highlight both the antagonistic and agonistic effects of the NF-κB signaling pathway on HIV-1 latency. Synergistic inducers acting 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.