Unknown

Dataset Information

0

Reactivation of latent HIV-1 by new semi-synthetic ingenol esters.


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-?, PMA and HMBA. ING B activated PKC isoforms followed by NF-?B nuclear translocation. As virus reactivation is dependent on intact NF-?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 T1. 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.

SUBMITTER: Pandelo Jose D 

PROVIDER: S-EPMC4383768 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

altmetric image

Publications


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-α, PMA and HMBA. ING B activated PKC isoforms followed by NF-κB nuclear translocation. As virus r  ...[more]

Similar Datasets

| S-EPMC5573388 | biostudies-literature
| S-EPMC4870680 | biostudies-literature
| S-EPMC3523124 | biostudies-literature
| S-EPMC4392775 | biostudies-literature
| S-EPMC6483647 | biostudies-literature
| S-EPMC9500661 | biostudies-literature
| S-EPMC4504130 | biostudies-literature
| S-EPMC5709488 | biostudies-literature
| S-EPMC4774903 | biostudies-literature
| S-EPMC5923069 | biostudies-literature