Patient-adapted, specific activation of HIV-1 by customized TAL effectors (TALEs), a proof of principle study

Autor: Rene Geissler, Nancy Funk, Jan van Lunzen, Jan Chemnitz, Martina Behrens, Sven-Erik Behrens, Ilona Hauber, Heidi Baum, Ivonne Renner, Helga Hofmann-Sieber, Annekatrin Richter, Jens Boch, Joachim Hauber
Rok vydání: 2015
Předmět:
Zdroj: Virology. 486
ISSN: 1096-0341
Popis: The major obstacle to cure infections with human immunodeficiency virus (HIV-1) is integrated proviral genomes, which are not eliminated by antiretroviral therapies (ART). Treatment approaches with latency-reversing agents (LRAs) aim at inducing provirus expression to tag latently-infected cells for clearance through viral cytopathic effects or cytotoxic T cell (CTL) responses. However, the currently tested LRAs reveal evident drawbacks as gene expression is globally induced and viral outgrowth is insecure. Here, we present transcription activator-like effector (TALE) proteins as potent tools to activate HIV-1 specifically. The large variety of circulating HIV-1 strains and, accordingly, integrated proviruses was addressed by the programmable DNA-specificity of TALEs. Using customized engineered TALEs, a substantial transcription activation and viral outgrowth was achieved with cells obtained from different HIV-1 patients. Our data suggest that TALEs may be useful tools in future strategies aimed at removing HIV-1 reservoirs.
Databáze: OpenAIRE