title: Patient-adapted, specific activation of HIV-1 by customized TAL effectors (TALEs), a proof of principle study.
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.
authors.affiliation: Institute of Biochemistry and Biotechnology, Section Microbial Biotechnology, Martin Luther University Halle-Wittenberg, Faculty of Life Sciences (NFI), Halle/Saale, Germany.
authors.forename: Rene
authors.initials: R
authors.lastname: Geissler
authors.affiliation: Heinrich Pette Institute-Leibniz Institute for Experimental Virology, Hamburg, Germany.
authors.forename: Ilona
authors.initials: I
authors.lastname: Hauber
authors.affiliation: Institute of Biochemistry and Biotechnology, Section Microbial Biotechnology, Martin Luther University Halle-Wittenberg, Faculty of Life Sciences (NFI), Halle/Saale, Germany.
authors.forename: Nancy
authors.initials: N
authors.lastname: Funk
authors.affiliation: Institute of Biology, Department of Genetics, Martin Luther University Halle-Wittenberg, Faculty of Life Sciences (NFI), Halle/Saale, Germany.
authors.forename: Annekatrin
authors.initials: A
authors.lastname: Richter
authors.affiliation: Institute of Biochemistry and Biotechnology, Section Microbial Biotechnology, Martin Luther University Halle-Wittenberg, Faculty of Life Sciences (NFI), Halle/Saale, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Behrens
authors.affiliation: Institute of Biochemistry and Biotechnology, Section Microbial Biotechnology, Martin Luther University Halle-Wittenberg, Faculty of Life Sciences (NFI), Halle/Saale, Germany.
authors.forename: Ivonne
authors.initials: I
authors.lastname: Renner
authors.affiliation: Heinrich Pette Institute-Leibniz Institute for Experimental Virology, Hamburg, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Chemnitz
authors.affiliation: Heinrich Pette Institute-Leibniz Institute for Experimental Virology, Hamburg, Germany.
authors.forename: Helga
authors.initials: H
authors.lastname: Hofmann-Sieber
authors.affiliation: Institute of Biochemistry and Biotechnology, Section Microbial Biotechnology, Martin Luther University Halle-Wittenberg, Faculty of Life Sciences (NFI), Halle/Saale, Germany.
authors.forename: Heidi
authors.initials: H
authors.lastname: Baum
authors.affiliation: Heinrich Pette Institute-Leibniz Institute for Experimental Virology, Hamburg, Germany; German Center for Infection Research (DZIF), Partner Site Hamburg, Hamburg, Germany; University Medical Center Hamburg-Eppendorf, Infectious Diseases Unit, Hamburg, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: van Lunzen
authors.affiliation: Institute of Biology, Department of Genetics, Martin Luther University Halle-Wittenberg, Faculty of Life Sciences (NFI), Halle/Saale, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Boch
authors.affiliation: Heinrich Pette Institute-Leibniz Institute for Experimental Virology, Hamburg, Germany; German Center for Infection Research (DZIF), Partner Site Hamburg, Hamburg, Germany.
authors.forename: Joachim
authors.initials: J
authors.lastname: Hauber
authors.affiliation: Institute of Biochemistry and Biotechnology, Section Microbial Biotechnology, Martin Luther University Halle-Wittenberg, Faculty of Life Sciences (NFI), Halle/Saale, Germany. Electronic address: sven.behrens@biochemtech.uni-halle.de.
authors.forename: Sven-Erik
authors.initials: SE
authors.lastname: Behrens
mesh_terms: D015967:Gene Expression Regulation, Viral; D015658:HIV Infections / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D005810:Multigene Family; D013045:Species Specificity; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism; D014775:Virus Activation; D017735:Virus Latency
chemical_list: D014157:Transcription Factors; D014764:Viral Proteins