Literature DB >> 21471244

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

Sifei Xing1, 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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Year:  2011        PMID: 21471244      PMCID: PMC3126325          DOI: 10.1128/JVI.02033-10

Source DB:  PubMed          Journal:  J Virol        ISSN: 0022-538X            Impact factor:   5.103


  16 in total

1.  Long-term follow-up studies confirm the stability of the latent reservoir for HIV-1 in resting CD4+ T cells.

Authors:  Janet D Siliciano; Joleen Kajdas; Diana Finzi; Thomas C Quinn; Karen Chadwick; Joseph B Margolick; Colin Kovacs; Stephen J Gange; Robert F Siliciano
Journal:  Nat Med       Date:  2003-05-18       Impact factor: 53.440

2.  Quantification of latent tissue reservoirs and total body viral load in HIV-1 infection.

Authors:  T W Chun; L Carruth; D Finzi; X Shen; J A DiGiuseppe; H Taylor; M Hermankova; K Chadwick; J Margolick; T C Quinn; Y H Kuo; R Brookmeyer; M A Zeiger; P Barditch-Crovo; R F Siliciano
Journal:  Nature       Date:  1997-05-08       Impact factor: 49.962

3.  Presence of an inducible HIV-1 latent reservoir during highly active antiretroviral therapy.

Authors:  T W Chun; L Stuyver; S B Mizell; L A Ehler; J A Mican; M Baseler; A L Lloyd; M A Nowak; A S Fauci
Journal:  Proc Natl Acad Sci U S A       Date:  1997-11-25       Impact factor: 11.205

4.  Identification of a reservoir for HIV-1 in patients on highly active antiretroviral therapy.

Authors:  D Finzi; M Hermankova; T Pierson; L M Carruth; C Buck; R E Chaisson; T C Quinn; K Chadwick; J Margolick; R Brookmeyer; J Gallant; M Markowitz; D D Ho; D D Richman; R F Siliciano
Journal:  Science       Date:  1997-11-14       Impact factor: 47.728

Review 5.  HIV persistence and the prospect of long-term drug-free remissions for HIV-infected individuals.

Authors:  Didier Trono; Carine Van Lint; Christine Rouzioux; Eric Verdin; Françoise Barré-Sinoussi; Tae-Wook Chun; Nicolas Chomont
Journal:  Science       Date:  2010-07-09       Impact factor: 47.728

6.  Recovery of replication-competent HIV despite prolonged suppression of plasma viremia.

Authors:  J K Wong; M Hezareh; H F Günthard; D V Havlir; C C Ignacio; C A Spina; D D Richman
Journal:  Science       Date:  1997-11-14       Impact factor: 47.728

Review 7.  A review of the pharmacokinetics and pharmacodynamics of disulfiram and its metabolites.

Authors:  B Johansson
Journal:  Acta Psychiatr Scand Suppl       Date:  1992

8.  Elimination kinetics of disulfiram in alcoholics after single and repeated doses.

Authors:  M D Faiman; J C Jensen; R B Lacoursiere
Journal:  Clin Pharmacol Ther       Date:  1984-10       Impact factor: 6.875

9.  Disulfiram and diethyldithiocarbamate intoxication affects the storage and release of striatal dopamine.

Authors:  A Vaccari; P L Saba; S Ruiu; M Collu; P Devoto
Journal:  Toxicol Appl Pharmacol       Date:  1996-07       Impact factor: 4.219

10.  Disulfiram and erythrocyte aldehyde dehydrogenase inhibition.

Authors:  J F Towell; J K Cho; B L Roh; R I Wang
Journal:  Clin Pharmacol Ther       Date:  1983-04       Impact factor: 6.875

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  115 in total

Review 1.  HIV reservoirs and strategies for eradication.

Authors:  Miranda Z Smith; Fiona Wightman; Sharon R Lewin
Journal:  Curr HIV/AIDS Rep       Date:  2012-03       Impact factor: 5.071

2.  Potential of Radiation-Induced Cellular Stress for Reactivation of Latent HIV-1 and Killing of Infected Cells.

Authors:  Sergey Iordanskiy; Fatah Kashanchi
Journal:  AIDS Res Hum Retroviruses       Date:  2016-02       Impact factor: 2.205

3.  Post-treatment control of HIV infection.

Authors:  Jessica M Conway; Alan S Perelson
Journal:  Proc Natl Acad Sci U S A       Date:  2015-04-13       Impact factor: 11.205

4.  Disulfiram metabolite S-methyl-N,N-diethylthiocarbamate quantitation in human plasma with reverse phase ultra performance liquid chromatography and mass spectrometry.

Authors:  Jill Hochreiter; Elinore F McCance-Katz; Jill Lapham; Qing Ma; Gene D Morse
Journal:  J Chromatogr B Analyt Technol Biomed Life Sci       Date:  2012-04-01       Impact factor: 3.205

Review 5.  HIV-1 transcription and latency: an update.

Authors:  Carine Van Lint; Sophie Bouchat; Alessandro Marcello
Journal:  Retrovirology       Date:  2013-06-26       Impact factor: 4.602

6.  TLR7 agonists induce transient viremia and reduce the viral reservoir in SIV-infected rhesus macaques on antiretroviral therapy.

Authors:  So-Yon Lim; Christa E Osuna; Peter T Hraber; Joe Hesselgesser; Jeffrey M Gerold; Tiffany L Barnes; Srisowmya Sanisetty; Michael S Seaman; Mark G Lewis; Romas Geleziunas; Michael D Miller; Tomas Cihlar; William A Lee; Alison L Hill; James B Whitney
Journal:  Sci Transl Med       Date:  2018-05-02       Impact factor: 17.956

7.  Short communication: SAHA (vorinostat) induces CDK9 Thr-186 (T-loop) phosphorylation in resting CD4+ T cells: implications for reactivation of latent HIV.

Authors:  Rajesh Ramakrishnan; Hongbing Liu; Andrew P Rice
Journal:  AIDS Res Hum Retroviruses       Date:  2015-01       Impact factor: 2.205

8.  BET bromodomain-targeting compounds reactivate HIV from latency via a Tat-independent mechanism.

Authors:  Daniela Boehm; Vincenzo Calvanese; Roy D Dar; Sifei Xing; Sebastian Schroeder; Laura Martins; Katherine Aull; Pao-Chen Li; Vicente Planelles; James E Bradner; Ming-Ming Zhou; Robert F Siliciano; Leor Weinberger; Eric Verdin; Melanie Ott
Journal:  Cell Cycle       Date:  2012-02-01       Impact factor: 4.534

9.  Histone deacetylase inhibitors (HDACis) that release the positive transcription elongation factor b (P-TEFb) from its inhibitory complex also activate HIV transcription.

Authors:  Koen Bartholomeeusen; Koh Fujinaga; Yanhui Xiang; B Matija Peterlin
Journal:  J Biol Chem       Date:  2013-03-28       Impact factor: 5.157

10.  Short-term administration of disulfiram for reversal of latent HIV infection: a phase 2 dose-escalation study.

Authors:  Julian H Elliott; James H McMahon; Christina C Chang; Sulggi A Lee; Wendy Hartogensis; Namandje Bumpus; Rada Savic; Janine Roney; Rebecca Hoh; Ajantha Solomon; Michael Piatak; Robert J Gorelick; Jeff Lifson; Peter Bacchetti; Steven G Deeks; Sharon R Lewin
Journal:  Lancet HIV       Date:  2015-11-17       Impact factor: 12.767

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