• 作者：Mateusz Stoszko^a ; ¹ ; Elisa De Crignis^a ; ¹ ; Casper Rokx^c ; Mir Mubashir Khalid^a ; Cynthia Lungu^a ; Robert-Jan Palstra^a ; Tsung Wai Kan^a ; Charles Boucher^d ; Annelies Verbon^c ; Emily C. Dykhuizen^b ; Tokameh Mahmoudi^a ; ^{t.mahmoudi@erasmusmc.nl" class="auth_mail" title="E-mail the corresponding author}
• 关键词：BAF250a ; BAF Associated Factor 250 a ; BAF ; BRG-Brahma Associated Factors ; BAFi ; BAF inhibitor ; bp ; base pairs ; BRG-1 ; Brahma Related Gene 1 ; CAPE ; caffeic acid phenetyl esther ; cART ; combination Antiretroviral Therapy ; ChIP ; Chromatin Immunoprecipitation ; CycA ; Cyclophilin A ; DHS-1 ; DNase Hypersensitive Site 1 ; ES cells ; embryonic stem cells ; FAIRE ; Formaldehyde Assisted Isolation of Regulatory Elements ; FBS ; Fetal Bovine Serum ; GFP ; Green Fluorescent Protein ; HDAC ; histone deacetylase ; HIV-1 ; h
• 刊名：EBioMedicine
• 出版年：2016
• 出版时间：January 2016
• 年：2016
• 卷：3
• 期：Complete
• 页码：108-121
• 全文大小：2002 K

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BAF complex inhibitors (BAFi's) activate latent HIV-1 in cell line models of latency.

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BAFi's in combination with HDAC inhibitors and PKC activators synergistically activate latent HIV-1.

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The BAFi's PYR and CAPE reverse HIV-1 latency in primary cell models of latency and in cells obtained from HIV-1 patients.

Access to Combination antiretroviral therapy (cART) has made HIV-1 infection a chronic disease. However, cART is not curative, as a small number of infected cells harboring silent virus with potential to renew the infection persist despite cART. Efforts to cure HIV-1 include activation of these latent cells, making them susceptible to immune clearance. Here we describe the activity of BAF inhibitors in HIV-1 activation in in vitro models of HIV-1 latency as well as in cells obtained from HIV-1 infected patient volunteers. Our data highlight the clinical potential of BAF inhibitors for inclusion in combinatorial therapy to reverse HIV-1 latency.