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
Book Volume: 25
Pages Range: 858-872.e13
Journal Issue: 6
DOI: 10.1016/j.chom.2019.05.002
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.
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://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.
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