Disulfiram reactivates latent HIV-1 in a Bcl-2-transduced primary CD4+ T cell model without inducing global T cell activation
Sifei Xing, Cynthia K Bullen, Neeta S Shroff, Liang Shan, Hung-Chih Yang, Jordyn L Manucci, Shridhar Bhat, Hao Zhang, Joseph B Margolick, Thomas C Quinn, David M Margolis, Janet D Siliciano, Robert F Siliciano, Sifei Xing, Cynthia K Bullen, Neeta S Shroff, Liang Shan, Hung-Chih Yang, Jordyn L Manucci, Shridhar Bhat, Hao Zhang, Joseph B Margolick, Thomas C Quinn, David M Margolis, Janet D Siliciano, Robert F Siliciano
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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Source: PubMed