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IFI16 Targets Sp1 to Suppress HIV-1 Transcription and ReactivationLatency

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发表于 2019-8-21 13:02:00 | 显示全部楼层 |阅读模式
IFI16 Targets the Transcription Factor Sp1 to Suppress HIV-1 Transcription and Latency Reactivation

Highlights

IFI16 targets Sp1 to restrict HIV-1 transcription and LINE-1 retrotransposition



The N-terminal pyrin and NLS domains of IFI16 are sufficient for restriction



Sp1 inhibition by IFI16 or Mithramycin A suppresses reactivation of latent HIV-1



Murine homologs of IFI16 restrict retroviral replication in vitro and in vivo




Summary
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.

https://www.sciencedirect.com/science/article/pii/S1931312819302471


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