ArticlePLoS pathogens2020
Nuclear PYHIN proteins target the host transcription factor Sp1 thereby restricting HIV-1 in human macrophages and CD4+ T cells.
Article in PLoS pathogens, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 39 citations in OpenAlex.
- Antiviral Inflammasomes and How to Find Them.Viruses · 2026Review
- PYHIN proteins: guardians or contributors to hepatitis B virus pathogenesis?Frontiers in immunology · 2026Review
- Article
- Cellular senescence-associated gene IFI16 promotes HMOX1-dependent evasion of ferroptosis and radioresistance in glioblastoma.Nature communications · 2025Article
- Catch me if you can: viral nucleic acids to host sensors.Frontiers in immunology · 2025Review
- Host cell glycosylation selects for infection with CCR5- versus CXCR4-tropic HIV-1.Nature microbiology · 2024Article
- Antiviral factors and their counteraction by HIV-1: many uncovered and more to be discovered.Journal of molecular cell biology · 2024Review
- RPLP1 restricts HIV-1 transcription by disrupting C/EBPβ binding to the LTR.Nature communications · 2024Article
- Review
- Article
- HIV-1 Vpr Functions in Primary CD4Viruses · 2024Review
- MNDA, a PYHIN factor involved in transcriptional regulation and apoptosis control in leukocytes.Frontiers in immunology · 2024Review
- Myeloid cell-expressed MNDA enhances M2 polarization to facilitate the metastasis of hepatocellular carcinoma.International journal of biological sciences · 2024Article
- Inflammasomes as mediators of inflammation in HIV-1 infection.Translational research : the journal of laboratory and clinical medicine · 2023Review
- Functions and roles of IFIX, a member of the human HIN-200 family, in human diseases.Molecular and cellular biochemistry · 2022Review
- Myeloid cell nuclear differentiation antigen controls the pathogen-stimulated type I interferon cascade in human monocytes by transcriptional regulation of IRF7.Nature communications · 2022Article
- Interferon-inducible protein, IFIX, has tumor-suppressive effects in oral squamous cell carcinoma.Scientific reports · 2021Article
- Induction of trained immunity by influenza vaccination - impact on COVID-19.PLoS pathogens · 2021Observational
- An additional NF-κB site allows HIV-1 subtype C to evade restriction by nuclear PYHIN proteins.Cell reports · 2021Article
- pMGF505-7R determines pathogenicity of African swine fever virus infection by inhibiting IL-1β and type I IFN production.PLoS pathogens · 2021Article
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Authors and funding
17 authors at 5 institutions in 1 country.
Funding
Abstract
Members of the family of pyrin and HIN domain containing (PYHIN) proteins play an emerging role in innate immunity. While absent in melanoma 2 (AIM2) acts a cytosolic sensor of non-self DNA and plays a key role in inflammasome assembly, the γ-interferon-inducible protein 16 (IFI16) restricts retroviral gene expression by sequestering the transcription factor Sp1. Here, we show that the remaining two human PYHIN proteins, i.e. myeloid cell nuclear differentiation antigen (MNDA) and pyrin and HIN domain family member 1 (PYHIN1 or IFIX) share this antiretroviral function of IFI16. On average, knock-down of each of these three nuclear PYHIN proteins increased infectious HIV-1 yield from human macrophages by more than an order of magnitude. Similarly, knock-down of IFI16 strongly increased virus transcription and production in primary CD4+ T cells. The N-terminal pyrin domain (PYD) plus linker region containing a nuclear localization signal (NLS) were generally required and sufficient for Sp1 sequestration and anti-HIV-1 activity of IFI16, MNDA and PYHIN1. Replacement of the linker region of AIM2 by the NLS-containing linker of IFI16 resulted in a predominantly nuclear localization and conferred direct antiviral activity to AIM2 while attenuating its ability to form inflammasomes. The reverse change caused nuclear-to-cytoplasmic relocalization of IFI16 and impaired its antiretroviral activity but did not result in inflammasome assembly. We further show that the Zn-finger domain of Sp1 is critical for the interaction with IFI16 supporting that pyrin domains compete with DNA for Sp1 binding. Finally, we found that human PYHIN proteins also inhibit Hepatitis B virus and simian vacuolating virus 40 as well as the LINE-1 retrotransposon. Altogether, our data show that IFI16, PYHIN1 and MNDA restrict HIV-1 and other viral pathogens by interfering with Sp1-dependent gene expression and support an important role of nuclear PYHIN proteins in innate antiviral immunity.
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