Disulfiram Reactivates Latent HIV-1 in a Bcl-2-Transduced Primary CD4 + T Cell Model without Inducing Global T Cell Activation

Author:

Xing Sifei12,Bullen Cynthia K.1,Shroff Neeta S.3,Shan Liang12,Yang Hung-Chih1,Manucci Jordyn L.1,Bhat Shridhar2,Zhang Hao4,Margolick Joseph B.4,Quinn Thomas C.15,Margolis David M.6,Siliciano Janet D.1,Siliciano Robert F.13

Affiliation:

1. Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland

2. Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland

3. Howard Hughes Medical Institute, Baltimore, Maryland

4. Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland

5. Division of Intramural Research, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland

6. University of North Carolina, Chapel Hill, North Carolina

Abstract

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.

Publisher

American Society for Microbiology

Subject

Virology,Insect Science,Immunology,Microbiology

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