ArticlePLoS pathogens2022
Free ISG15 inhibits Pseudorabies virus infection by positively regulating type I IFN signaling.
Article in PLoS pathogens, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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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.
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Who cites it
22 citing papers in PubMed, 26 citations in OpenAlex.
- Nectin4 restricts pseudorabies virus infection by blocking gD-Nectin1 interaction.Journal of virology · 2026Article
- A Natural Peptide from the American Cockroach Suppresses Feline Infectious Peritonitis Virus.Biology · 2026Article
- The Emerging Role of Interferon-Stimulated Gene 15 (ISG15) in Pregnancy-Related Disorders.Reproductive sciences (Thousand Oaks, Calif.) · 2026Review
- Article
- Cannabidiol triggers fatty acids β-oxidation mediated by Stat2 to facilitate intestinal stem cells regeneration post radiation.Experimental & molecular medicine · 2026Article
- ISG15-driven immune modulation and tumor progression in breast cancer metastasis: insights from single-cell and spatial transcriptomics.BMC medicine · 2026Article
- Beyond Viral Restriction: The Metabolic Dimensions of Interferon-Stimulated Genes in Antiviral Immunity.Viruses · 2026Review
- Silencing of Ifi27l2a Attenuates Inflammation After Spinal Cord Injury by Regulating Microglial Polarization via JAK2/STAT3 Signaling.Molecular neurobiology · 2026Article
- Organelle-centered ISG15 biology: distinguishing covalent ISGylation from interferon-associated responses.Frontiers in immunology · 2026Review
- Expression Profiles of lncRNAs and mRNAs in the Mouse Brain Infected with Pseudorabies Virus: A Bioinformatic Analysis.Viruses · 2025Article
- Article
- The evolving mpox threat (2022-2024): clade dynamics, immune evasion, and escalating global health challenges.Frontiers in cellular and infection microbiology · 2025Review
- Evasion of the Antiviral Innate Immunity by PRV.International journal of molecular sciences · 2024Review
- STRAP upregulates antiviral innate immunity against PRV by targeting TBK1.Virology journal · 2024Article
- Nuclear translocation of ISG15 regulated by PPP2R2B inhibits cisplatin resistance of bladder cancer.Cellular and molecular life sciences : CMLS · 2024Article
- ISGylation of DRP1 closely balances other post-translational modifications to mediate mitochondrial fission.Cell death & disease · 2024Article
- Unveiling the Multifaceted Roles of ISG15: From Immunomodulation to Therapeutic Frontiers.Vaccines · 2024Review
- Identification of host factors for livestock and poultry viruses: genome-wide screening technology based on the CRISPR system.Frontiers in microbiology · 2024Review
- ISG15: its roles in SARS-CoV-2 and other viral infections.Trends in microbiology · 2023Review
- Research Progress of Porcine Reproductive and Respiratory Syndrome Virus NSP2 Protein.Viruses · 2023Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Interferon-stimulated gene 15 (ISG15) is strongly upregulated during viral infections and exerts pro-viral or antiviral actions. While many viruses combat host antiviral defenses by limiting ISG expression, PRV infection notably increases expression of ISG15. However, studies on the viral strategies to regulate ISG15-mediated antiviral responses are limited. Here, we demonstrate that PRV-induced free ISG15 and conjugated proteins accumulation require viral gene expression. Conjugation inhibition assays showed that ISG15 imposes its antiviral effects via unconjugated (free) ISG15 and restricts the viral release. Knockout of ISG15 in PK15 cells interferes with IFN-β production by blocking IRF3 activation and promotes PRV replication. Mechanistically, ISG15 facilitates IFNα-mediated antiviral activity against PRV by accelerating the activation and nuclear translocation of STAT1 and STAT2. Furthermore, ISG15 facilitated STAT1/STAT2/IRF9 (ISGF3) formation and ISGF3-induced IFN-stimulated response elements (ISRE) activity for efficient gene transcription by directly interacting with STAT2. Significantly, ISG15 knockout mice displayed enhanced susceptibility to PRV, as evidenced by increased mortality and viral loads, as well as more severe pathology caused by excessive production of the inflammatory cytokines. Our studies establish the importance of free ISG15 in IFNα-induced antiviral immunity and in the control of viral infections.
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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.