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Title: Reactivation of latent HIV-1 by new semi-synthetic ingenol esters
Authors: Jose, Diego Pandelo
Bartholomeeusen, Koen
da Cunha, Rodrigo Delvecchio
Abreu, Celina Monteiro
Glinski, Jan
Ferreira da Costa, Thais Barbizan
Mello Bacchi Rabay, Ana Flavia
Pianowski Filho, Luiz Francisco
Dudycz, Lech W.
Ranga, Udaykumar
Peterlin, Boris Matija
Pianowski, Luiz Francisco
Tanuri, Amilcar
Aguiar, Renato Santana
Keywords: Virology
Nf-Kappa B
Resting Cells
Immunodeficiency-Virus Type-1
Suberoylanilide Hydroxamic Acid
Active Antiretroviral Therapy
Subtype C
Deacetylase Inhibitors
Issue Date: 2014
Publisher: Academic Press Inc Elsevier Science
Citation: Jose, DP; Bartholomeeusen, K; da Cunha, RD; Abreu, CM; Glinski, J; da Costa, TBF; Rabay, AFMB; Pianowski, LF; Dudycz, LW; Ranga, U; Peterlin, BM; Pianowski, LF; Tanuri, A; Aguiar, RS, Reactivation of latent HIV-1 by new semi-synthetic ingenol esters. Virology 2014, 462, 328-339,
Abstract: The ability of HIV to establish long-lived latent infection is mainly due to transcriptional silencing of viral genome in resting memory T lymphocytes. Here, we show that new semi-synthetic ingenol esters reactivate latent HIV reservoirs. Amongst the tested compounds, 3-caproyl-ingenol (ING B) was more potent in reactivating latent HIV than known activators such as SAHA, ingenol 3,20-dibenzoate, TNF-alpha, PMA and HMBA. ING B activated PKC isoforms followed by NF-kappa B nuclear translocation. As virus reactivation is dependent on intact NF-kappa B binding sites in the LTR promoter region ING B, we have shown that. ING B was able to reactivate virus transcription in primary HIV-infected resting cells up to 12 fold and up to 25 fold in combination with SAHA. Additionally, ING B promoted up-regulation of P-TEFb subunits CDK9/Cyclin TI. The role of ING B on promoting both transcription initiation and elongation makes this compound a strong candidate for an anti-HIV latency drug combined with suppressive HAART. (C) 2014 Elsevier Inc. All rights reserved.
Description: Restricted Access
ISSN: 0042-6822
Appears in Collections:Research Papers (Ravi Manjithaya)

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