title: Dilazep synergistically reactivates latent HIV-1 in latently infected cells.
abstract: The long-lived latently infected cells persist in spite of prolonged highly active anti-retroviral therapy and present a major barrier to a cure of human immunodeficiency virus type 1 (HIV-1) infection. Elimination of this reservoir requires reactivation of the latent virus. None of the current agents can safely and effectively reactivate latent HIV-1 reservoirs. Dilazep, a nucleoside transport inhibitor, is used to treat ischemic dysfunction. However, little is known about the effect of dilazep in inducing HIV expression in latently infected cells. Using the Jurkat T cell model of HIV-1 latency, we found that dilazep effectively reactivates latent HIV-1 gene expression in a dose manner. We observed that dilazep synergistically reactivated latent HIV-1 transcription with valproic acid. We also found that dilazep activates viral latency without inducing cell surface activation markers CD25 and CD69 activation. In summary, dilazep, alone or in combination with VPA, could be useful in future eradication strategies.
authors.affiliation: School of Life Sciences, Institute of Genetics, Fudan University, Shanghai, 200433, China.
authors.forename: Hanxian
authors.initials: H
authors.lastname: Zeng
authors.forename: Sijie
authors.initials: S
authors.lastname: Liu
authors.forename: Pengfei
authors.initials: P
authors.lastname: Wang
authors.forename: Xiying
authors.initials: X
authors.lastname: Qu
authors.forename: Haiyan
authors.initials: H
authors.lastname: Ji
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Wang
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Zhu
authors.forename: Zhishuo
authors.initials: Z
authors.lastname: Song
authors.forename: Xinyi
authors.initials: X
authors.lastname: Yang
authors.forename: Zhongjun
authors.initials: Z
authors.lastname: Ma
authors.forename: Huanzhang
authors.initials: H
authors.lastname: Zhu
mesh_terms: D004109:Dilazep / Q000494:pharmacology*; D004197:Disease Reservoirs / Q000821:virology*; D004357:Drug Synergism; D005434:Flow Cytometry; D049452:Green Fluorescent Proteins; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D019169:Jurkat Cells; D014635:Valproic Acid / Q000494:pharmacology; D014775:Virus Activation / Q000187:drug effects*; D017735:Virus Latency / Q000502:physiology*
chemical_list: D049452:Green Fluorescent Proteins; D014635:Valproic Acid; D004109:Dilazep
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