Transcriptional Suppression of In Vitro-Integrated Human Immunodeficiency Virus Type 1 Does Not Correlate with Proviral DNA Methylation

Pion, Marjorie; Jordan, Albert; Biancotto, Angélique; Dequiedt, Samuel; Gondois-Rey, Françoise; Rondeau, Sophie; Vigne, Robert; Hejnar, Jiřı́; Verdin, Eric; Hirsch, Ivan

doi:10.1128/jvi.77.7.4025-4032.2003

Cited by 48 publications

(43 citation statements)

References 50 publications

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“…Up to 30% of these cells are infected productively (20,34). Several soluble factors responsible for productive infection of resting CD4 ϩ T cells have been identified recently (41,42,46).…”

Section: Discussionmentioning

confidence: 99%

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Dual Role of Prostratin in Inhibition of Infection and Reactivation of Human Immunodeficiency Virus from Latency in Primary Blood Lymphocytes and Lymphoid Tissue

Biancotto

Grivel

Gondois-Rey

et al. 2004

J Virol

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Section: Discussionmentioning

confidence: 99%

“…ϩ T cells that harbored the HIV-1 genome (20,34). We stimulated these cells with prostratin, TPA, or anti-CD3/CD28 antibodies in the presence of 10 M AZT and 5 M nevirapine.…”

Section: Vol 78 2004 Effect Of Prostratin On Hiv Infection and Latementioning

confidence: 99%

Dual Role of Prostratin in Inhibition of Infection and Reactivation of Human Immunodeficiency Virus from Latency in Primary Blood Lymphocytes and Lymphoid Tissue

Biancotto

Grivel

Gondois-Rey

et al. 2004

J Virol

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“…Following integration of the virus, a restrictive histone code is established at the HIV-1 promoter (long terminal repeat [LTR]) and suppresses HIV-1 gene expression (54,56,74). DNA methylation of the viral LTR could stabilize latent infection (9,10).…”

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confidence: 99%

Selected Drugs with Reported Secondary Cell-Differentiating Capacity Prime Latent HIV-1 Infection for Reactivation

Shishido

Wolschendorf

Duverger

et al. 2012

J Virol

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Reactivation of latent HIV-1 infection is considered our best therapeutic means to eliminate the latent HIV-1 reservoir. Past therapeutic attempts to systemically trigger HIV-1 reactivation using single drugs were unsuccessful. We thus sought to identify drug combinations consisting of one component that would lower the HIV-1 reactivation threshold and a synergistic activator. With aclacinomycin and dactinomycin, we initially identified two FDA-approved drugs that primed latent HIV-1 infection in T cell lines and in primary T cells for reactivation and facilitated complete reactivation at the population level. This effect was correlated not with the reported primary drug effects but with the cell-differentiating capacity of the drugs. We thus tested other cell-differentiating drugs/compounds such as cytarabine and aphidicolin and found that they also primed latent HIV-1 infection for reactivation. This finding extends the therapeutic promise of N ′- N ′-hexamethylene-bisacetamide (HMBA), another cell-differentiating agent that has been reported to trigger HIV-1 reactivation, into the group of FDA-approved drugs. To this end, it is also noteworthy that suberoylanilide hydroxamic acid (SAHA), a polar compound that was initially developed as a second-generation cell-differentiating agent using HMBA as a structural template and which is now marketed as the histone deacetylase (HDAC) inhibitor vorinostat, also has been reported to trigger HIV-1 reactivation. Our findings suggest that drugs with primary or secondary cell-differentiating capacity should be revisited as HIV-1-reactivating agents as some could potentially be repositioned as candidate drugs to be included in an induction therapy to trigger HIV-1 reactivation.

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“…Much interest has recently centered on developing HIV activation therapeutics that act epigenetically (reviewed in reference 14), such as via DNA methylation and histone acetylation. Some epigenetic agents are being studied in early clinical trials, but such strategies have the potential for significant off-target effects (OTE) (15)(16)(17)(18)(19)(20)(21), and some studies have suggested that these agents may have distinct activities in different latently infected model systems (22). Other studies have worked to identify new targets (23), such as genes that can be targeted to activate HIV expression when subjected to knockdown by RNA interference (RNAi) (24)(25)(26).…”

mentioning

confidence: 99%

Targeting IκB Proteins for HIV Latency Activation: the Role of Individual IκB and NF-κB Proteins

Fernàndez

Zaikos

Khan

et al. 2013

J Virol

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Transcriptional Suppression of In Vitro-Integrated Human Immunodeficiency Virus Type 1 Does Not Correlate with Proviral DNA Methylation

Cited by 48 publications

References 50 publications

Dual Role of Prostratin in Inhibition of Infection and Reactivation of Human Immunodeficiency Virus from Latency in Primary Blood Lymphocytes and Lymphoid Tissue

Dual Role of Prostratin in Inhibition of Infection and Reactivation of Human Immunodeficiency Virus from Latency in Primary Blood Lymphocytes and Lymphoid Tissue

Selected Drugs with Reported Secondary Cell-Differentiating Capacity Prime Latent HIV-1 Infection for Reactivation

Targeting IκB Proteins for HIV Latency Activation: the Role of Individual IκB and NF-κB Proteins

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