Molecular characterization, reactivation, and depletion of latent HIV
Molecular characterization, reactivation, and depletion of latent HIV
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DOI：
10.1016/s1074-7613(03)00236-x
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发表时间：
2003-09-01
期刊：
影响因子：
32.4
通讯作者：
Zack, JA
中科院分区：
文献类型：
--
作者：
Brooks, DG;Hamer, DH;Zack, JA
抗逆转录病毒疗法不能消除潜伏感染T细胞的小而长寿的群体中的HIV感染，这为治疗停止后的病毒复制提供了新的来源。对SCID-hu（Thy/Liv）小鼠中产生的单个潜伏感染细胞的分析表明，在潜伏状态下不产生功能性病毒RNA。再活化后，病毒表达显著增加，使感染的细胞对抗HIV免疫毒素敏感。用免疫毒素与激活病毒表达而不诱导细胞分裂的药物（IL-7或非肿瘤促进性佛波醇酯prostratin）联合治疗，耗尽了大部分潜伏性储库，使未感染的细胞能够对随后的共刺激做出反应。我们证明了激活潜伏病毒是抗病毒剂靶向治疗所必需的，并为未来根除潜伏病毒库的治疗策略提供了基础。
Antiretroviral therapy is unable to eliminate HIV infection in a small, long-lived population of latently infected T cells, providing a source for renewed viral replication following cessation of therapy. Analysis of individual latently infected cells generated in the SCID-hu (Thy/Liv) mouse demonstrated no functional viral RNA produced in the latent state. Following reactivation viral expression was dramatically increased, rendering the infected cells susceptible to an anti-HIV immunotoxin. Treatment with the immunotoxin in conjunction with agents that activate virus expression without inducing cell division (IL-7 or the non-tumor-promoting phorbol ester prostratin) depleted the bulk of the latent reservoir and left uninfected cells able to respond to subsequent costimulation. We demonstrate that activation of latent virus is required for targeting by antiviral agents and provide the basis for future therapeutic strategies to eradicate the latent reservoir.