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Latent HIV-1 TAR Regulates 7SK-responsive P-TEFb Target Genes and Targets Cellular Immune Responses in the Absence of Tat.

Authors
  • Eilebrecht, Sebastian1
  • Benecke, Bernd-Joachim2
  • Benecke, Arndt G3
  • 1 CNRS UMR8246, Université Pierre et Marie Curie, Paris 75005, France; ACSIOMA GmbH, Technologiezentrum Ruhr, Bochum 44799, Germany. Electronic address: [email protected] , (Germany)
  • 2 ACSIOMA GmbH, Technologiezentrum Ruhr, Bochum 44799, Germany. , (Germany)
  • 3 CNRS UMR8246, Université Pierre et Marie Curie, Paris 75005, France; Center for Innate Immunity and Immune Disease, University of Washington School of Medicine, Seattle, WA 98195, USA. Electronic address: [email protected] , (France)
Type
Published Article
Journal
Genomics, proteomics & bioinformatics
Publication Date
Oct 01, 2017
Volume
15
Issue
5
Pages
313–323
Identifiers
DOI: 10.1016/j.gpb.2017.05.003
PMID: 29037489
Source
Medline
Keywords
License
Unknown

Abstract

The transactivating response element (TAR) structure of the nascent HIV-1 transcript is critically involved in the recruitment of inactive positive transcription elongation factor b (P-TEFb) to the promoter proximal paused RNA polymerase II. The viral transactivator Tat is responsible for subsequent P-TEFb activation in order to start efficient viral transcription elongation. In the absence of the viral transactivator of transcription (Tat), e.g., during latency or in early stages of HIV transcription, TAR mediates an interaction of P-TEFb with its inhibitor hexamethylene bis-acetamide-inducible protein 1 (HEXIM1), keeping P-TEFb in its inactive form. In this study, we address the function of HIV-1 TAR in the absence of Tat by analyzing consequences of HIV-1 TAR overexpression on host cellular gene expression. An RNA chimera consisting of Epstein-Barr virus-expressed RNA 2 (EBER2) and HIV-1 TAR was developed to assure robust overexpression of TAR in HEK293 cells. The overexpression results in differential expression of more than 800 human genes. A significant proportion of these genes is involved in the suppression of cellular immune responses, including a significant set of 7SK-responsive P-TEFb target genes. Our findings identify a novel role for HIV-1 TAR in the absence of Tat, involving the interference with host cellular immune responses by targeting 7SK RNA-mediated gene expression and P-TEFb inactivation.

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