title: Disulfiram reactivates latent HIV-1 in a Bcl-2-transduced primary CD4+ T cell model without inducing global T cell activation.
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.
authors.affiliation: Department of Medicine, Johns Hopkins University School of Medicine, 720 Rutland Ave., Baltimore, MD 21205, USA.
authors.forename: Sifei
authors.initials: S
authors.lastname: Xing
authors.forename: Cynthia K
authors.initials: CK
authors.lastname: Bullen
authors.forename: Neeta S
authors.initials: NS
authors.lastname: Shroff
authors.forename: Liang
authors.initials: L
authors.lastname: Shan
authors.forename: Hung-Chih
authors.initials: HC
authors.lastname: Yang
authors.forename: Jordyn L
authors.initials: JL
authors.lastname: Manucci
authors.forename: Shridhar
authors.initials: S
authors.lastname: Bhat
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
authors.forename: Joseph B
authors.initials: JB
authors.lastname: Margolick
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Quinn
authors.forename: David M
authors.initials: DM
authors.lastname: Margolis
authors.forename: Janet D
authors.initials: JD
authors.lastname: Siliciano
authors.forename: Robert F
authors.initials: RF
authors.lastname: Siliciano
mesh_terms: D019380:Anti-HIV Agents / Q000627:therapeutic use; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000821:virology*; D002478:Cells, Cultured; D004221:Disulfiram / Q000494:pharmacology* / Q000627:therapeutic use; D019254:Genes, bcl-2; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000276:immunology / Q000502:physiology; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D014161:Transduction, Genetic; D014775:Virus Activation / Q000187:drug effects*; D017735:Virus Latency / Q000187:drug effects*
chemical_list: D019380:Anti-HIV Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D004221:Disulfiram