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

• Published in: Virology (New York, N.Y.) Vol. 486; pp. 248 - 254
• Main Authors: Geissler, Rene, Hauber, Ilona, Funk, Nancy, Richter, Annekatrin, Behrens, Martina, Renner, Ivonne, Chemnitz, Jan, Hofmann-Sieber, Helga, Baum, Heidi, van Lunzen, Jan, Boch, Jens, Hauber, Joachim, Behrens, Sven-Erik
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.12.2015
• Subjects: Gene Expression Regulation, Viral; HIV Infections - genetics; HIV Infections - metabolism; HIV Infections - virology; HIV-1 - genetics; HIV-1 - physiology; Humans; Infectious Disease; Multigene Family; Species Specificity; Transcription Factors - genetics; Transcription Factors - metabolism; Viral Proteins - genetics; Viral Proteins - metabolism; Virus Activation; Virus Latency
• ISSN: 0042-6822; 1096-0341
• DOI: 10.1016/j.virol.2015.09.018

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.