标题: IFI16 Targets Sp1 to Suppress HIV-1 Transcription and ReactivationLatency [打印本页] 作者: wwwkkk83 时间: 2019-8-21 13:02 标题: IFI16 Targets Sp1 to Suppress HIV-1 Transcription and ReactivationLatency IFI16 Targets the Transcription Factor Sp1 to Suppress HIV-1 Transcription and Latency Reactivation
Highlights
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IFI16 targets Sp1 to restrict HIV-1 transcription and LINE-1 retrotransposition
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The N-terminal pyrin and NLS domains of IFI16 are sufficient for restriction
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Sp1 inhibition by IFI16 or Mithramycin A suppresses reactivation of latent HIV-1
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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.