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

authored by

Rene Geissler, Ilona Hauber, Nancy Funk, Annekatrin Richter, Martina Behrens, Ivonne Renner, Jan Chemnitz, Helga Hofmann-Sieber, Heidi Baum, Jan van Lunzen, Jens Boch, Joachim Hauber, Sven Erik Behrens

Abstract

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.

External Organisation(s)

Martin Luther University Halle-Wittenberg
Heinrich Pette Institute - Leibniz Institute for Experimental Virology (HPI)
German Center for Infection Research (DZIF)
University Medical Center Hamburg-Eppendorf

Type

Article

Journal

Virology

Volume

486

Pages

248-254

No. of pages

7

ISSN

0042-6822

Publication date

12.2015

Publication status

Published

Peer reviewed

Yes

ASJC Scopus subject areas

Virology

Sustainable Development Goals

SDG 3 - Good Health and Well-being

Electronic version(s)

https://doi.org/10.1016/j.virol.2015.09.018 (Access: Open)