IFI16 Targets the Transcription Factor Sp1 to Suppress HIV-1 Transcription and Latency Reactivation
Hotter D, Bosso M, Jønsson KL, Krapp C, Stürzel CM, Das A, Littwitz-Salomon E, Berkhout B, Russ A, Wittmann S, Gramberg T, Zheng Y, Martins LJ, Planelles V, Jakobsen MR, Hahn BH, Dittmer U, Sauter D, Kirchhoff F (2019)
Publication Type: Journal article
Publication year: 2019
Journal
Book Volume: 25
Pages Range: 858-872.e13
Journal Issue: 6
DOI: 10.1016/j.chom.2019.05.002
Abstract
The interferon γ-inducible protein 16 (IFI16) is known as immune sensor of retroviral DNA intermediates. We show that IFI16 restricts HIV-1 independently of immune sensing by binding and inhibiting the host transcription factor Sp1 that drives viral gene expression. This antiretroviral activity and ability to bind Sp1 require the N-terminal pyrin domain and nuclear localization of IFI16, but not the HIN domains involved in DNA binding. Highly prevalent clade C HIV-1 strains are more resistant to IFI16 and less dependent on Sp1 than other HIV-1 subtypes. Furthermore, inhibition of Sp1 by IFI16 or pharmacologically by Mithramycin A suppresses reactivation of latent HIV-1 in CD4+ T cells. Finally, IFI16 also inhibits retrotransposition of LINE-1, known to engage Sp1, and murine IFI16 homologs restrict Friend retrovirus replication in mice. Thus, IFI16 restricts retroviruses and retrotransposons by interfering with Sp1-dependent gene expression, and evasion from this restriction may facilitate spread of HIV-1 subtype C.
Authors with CRIS profile
Involved external institutions
Universitätsklinikum Ulm
Germany (DE)
University of Utah
United States (USA) (US)
University of Pennsylvania
United States (USA) (US)
Universitätsklinikum Essen
Germany (DE)
Aarhus University
Denmark (DK)
University of Amsterdam
Netherlands (NL)
Germany (DE)
University of Utah
United States (USA) (US)
University of Pennsylvania
United States (USA) (US)
Universitätsklinikum Essen
Germany (DE)
Aarhus University
Denmark (DK)
University of Amsterdam
Netherlands (NL)
How to cite
APA:
Hotter, D., Bosso, M., Jønsson, K.L., Krapp, C., Stürzel, C.M., Das, A.,... Kirchhoff, F. (2019). IFI16 Targets the Transcription Factor Sp1 to Suppress HIV-1 Transcription and Latency Reactivation. Cell Host & Microbe, 25(6), 858-872.e13. https://dx.doi.org/10.1016/j.chom.2019.05.002
MLA:
Hotter, Dominik, et al. "IFI16 Targets the Transcription Factor Sp1 to Suppress HIV-1 Transcription and Latency Reactivation." Cell Host & Microbe 25.6 (2019): 858-872.e13.
BibTeX: Download