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双硫仑在转染 Bcl-2 的原代 CD4+ T 细胞模型中重新激活潜伏的 HIV-1,而不诱导全局 T 细胞激活。

Disulfiram reactivates latent HIV-1 in a Bcl-2-transduced primary CD4+ T cell model without inducing global T cell activation.

机构信息

Department of Medicine, Johns Hopkins University School of Medicine, 720 Rutland Ave., Baltimore, MD 21205, USA.

出版信息

J Virol. 2011 Jun;85(12):6060-4. doi: 10.1128/JVI.02033-10. Epub 2011 Apr 6.

Abstract

Highly active antiretroviral therapy (HAART) can reduce plasma HIV-1 levels to below the detection limit. However, due to the latent reservoir in resting CD4(+) cells, HAART is not curative. Elimination of this reservoir is critical to curing HIV-1 infection. Agents that reactivate latent HIV-1 through nonspecific T cell activation are toxic. Here we demonstrate in a primary CD4(+) T cell model that the FDA-approved drug disulfiram reactivates latent HIV-1 without global T cell activation. The extent to which disulfiram reactivates latent HIV-1 in patient cells is unclear, but the drug alone or in combination may be useful in future eradication strategies.

摘要

高效抗逆转录病毒疗法(HAART)可降低血浆 HIV-1 水平至检测限以下。然而,由于静止 CD4(+)细胞中的潜伏储库,HAART 无法治愈。消除这种储库对于治愈 HIV-1 感染至关重要。通过非特异性 T 细胞激活来重新激活潜伏 HIV-1 的药物具有毒性。在这里,我们在原代 CD4(+)T 细胞模型中证明,FDA 批准的药物双硫仑可在不激活全 T 细胞的情况下重新激活潜伏 HIV-1。双硫仑在患者细胞中重新激活潜伏 HIV-1 的程度尚不清楚,但该药单独或联合使用可能对未来的清除策略有用。

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