Disulfiram reactivates latent HIV-1 in a Bcl-2-transduced primary CD4+ T cell model without inducing global T cell activation |
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Authors: | Xing Sifei Bullen Cynthia K Shroff Neeta S Shan Liang Yang Hung-Chih Manucci Jordyn L Bhat Shridhar Zhang Hao Margolick Joseph B Quinn Thomas C Margolis David M Siliciano Janet D Siliciano Robert F |
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Institution: | Department of Medicine, Johns Hopkins University School of Medicine, 720 Rutland Ave., Baltimore, MD 21205, USA. |
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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. |
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