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

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 proteins 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.
Type de document :
Article dans une revue
Genomics, Proteomics and Bioinformatics, Elsevier, 2017, 〈10.1016/j.gpb.2017.05.003〉
Liste complète des métadonnées

Littérature citée [54 références]  Voir  Masquer  Télécharger

http://hal.upmc.fr/hal-01617224
Contributeur : Gestionnaire Hal-Upmc <>
Soumis le : lundi 16 octobre 2017 - 13:56:38
Dernière modification le : jeudi 11 janvier 2018 - 06:28:16

Fichier

1-s2.0-S1672022917301407-main....
Fichiers produits par l'(les) auteur(s)

Licence


Distributed under a Creative Commons Paternité 4.0 International License

Identifiants

Collections

Citation

Sebastian Eilebrecht, Bernd-Joachim Benecke, Arndt Benecke. Latent HIV-1 TAR Regulates 7SK-responsive P-TEFb Target Genes and Targets Cellular Immune Responses in the Absence of Tat. Genomics, Proteomics and Bioinformatics, Elsevier, 2017, 〈10.1016/j.gpb.2017.05.003〉. 〈hal-01617224〉

Partager

Métriques

Consultations de la notice

74

Téléchargements de fichiers

16