ArticleJournal of leukocyte biology2018
CRISPR/Cas9 knockout of USP18 enhances type I IFN responsiveness and restricts HIV-1 infection in macrophages.
Article in Journal of leukocyte biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
36 citing papers in PubMed, 1 synthesis or guideline pooled it, 65 citations in OpenAlex.
- Trans-eQTL mapping prioritises USP18 as a negative regulator of interferon response at a lupus risk locus.Nature communications · 2025Pooled it
- Harnessing macrophage signaling pathways and scalable engineering for next-generation immunotherapies.Signal transduction and targeted therapy · 2026Review
- TDP-43 directly inhibits mRNA accumulation in neurites through modulation of mRNA stability.The EMBO journal · 2026Article
- The TRIM3/TLR3 axis overrides IFN-β feedback inhibition to suppress NSCLC progression.Cell death & disease · 2026Article
- Synergy between pluripotent stem cell-derived macrophages and self-renewing macrophages: Envisioning a promising avenue for the modelling and cell therapy of infectious diseases.Cell proliferation · 2025Review
- Interleukin-27-polarized HIV-resistant M2 macrophages are a novel subtype of macrophages that express distinct antiviral gene profiles in individual cells: implication for the antiviral effect via different mechanisms in the individual cell-dependent manner.Frontiers in immunology · 2025Article
- Manganese mediates antiviral effects by driving an ATM -TBK1 phosphorylation signaling pathway.Frontiers in immunology · 2025Article
- USP18 Is Associated with PD-L1 Antitumor Immunity and Improved Prognosis in Colorectal Cancer.Biomolecules · 2024Article
- Review
- USP18 enhances dengue virus replication by regulating mitochondrial DNA release.Scientific reports · 2023Article
- A Model of iPSC-Derived Macrophages withInternational journal of molecular sciences · 2023Article
- Enrichment of stem cell-derived pancreatic beta-like cells and controlled graft size through pharmacological removal of proliferating cells.Stem cell reports · 2023Article
- Molecular and cellular factors determining the functional pleiotropy of cytokines.The FEBS journal · 2023Review
- Article
- High-throughput identification of RNA localization elements in neuronal cells.Nucleic acids research · 2022Article
- Macrophages derived from pluripotent stem cells: prospective applications and research gaps.Cell & bioscience · 2022Review
- ISG15 deficiency restricts HIV-1 infection.PLoS pathogens · 2022Article
- Pathways Toward a Functional HIV-1 Cure: Balancing Promise and Perils of CRISPR Therapy.Methods in molecular biology (Clifton, N.J.) · 2022Review
- Article
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
The IFN-stimulated gene ubiquitin-specific proteinase 18 (USP18) encodes a protein that negatively regulates T1 IFN signaling via stearic inhibition of JAK1 recruitment to the IFN-α receptor 2 subunit (IFNAR2). Here, we demonstrate that USP18 expression is induced by HIV-1 in a T1 IFN-dependent manner. Experimental depletion of USP18 by clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) gene editing results in a significant restriction of HIV-1 replication in an induced pluripotent stem cell (iPSC)-derived macrophage model. In the absence of USP18, macrophages have increased responsiveness to stimulation with T1 IFNs with prolonged phosphorylation of STAT1 and STAT2 and increased expression of IFN-stimulated genes that are key for antiviral responses. Interestingly, HIV-1 requires some signaling through the T1 IFN receptor to replicate efficiently because a neutralizing antibody that inhibits T1 IFN activity reduces HIV-1 replication rate in monocyte-derived macrophages. USP18 induction by HIV-1 tunes the IFN response to optimal levels allowing for efficient transcription from the HIV-1 LTR promoter while minimizing the T1 IFN-induced antiviral response that would otherwise restrict viral replication and spread. Finally, iPSC and CRISPR/Cas9 gene targeting offer a powerful tool to study host factors that regulate innate immune responses.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.