ArticlePloS one2012
Cynoglossus semilaevis ISG15: a secreted cytokine-like protein that stimulates antiviral immune response in a LRGG motif-dependent manner.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 46 citations in OpenAlex.
- A fish-specific E3 ubiquitin ligase NHRE3 suppresses antiviral immunity by degrading ISG15 via ubiquitination.PLoS pathogens · 2026Article
- Extracellular Lipopolysaccharide Triggers the Release of Unconjugated Interferon-Stimulated Gene 15 (ISG15) Protein from Macrophages via Type-I Interferon/Caspase-4/Gasdermin-D Pathway.Pathogens (Basel, Switzerland) · 2026Article
- Identification of two ISG15 homologues involved in host immune response against RGNNV in Asian seabass (Fish and shellfish immunology reports · 2022Article
- Edwardsiella tarda TraT is an anti-complement factor and a cellular infection promoter.Communications biology · 2022Article
- Global profiling of megalocytivirus-induced proteins in tongue sole (Cynoglossus semilaevis) spleen identifies cellular processes essential to viral infection.Developmental and comparative immunology · 2019Article
- The Megalocytivirus RBIV Induces Apoptosis and MHC Class I Presentation in Rock BreamFrontiers in immunology · 2019Article
- Expression Analysis of Interferon-Stimulated Gene 15 in the Rock BreamDevelopment & reproduction · 2017Article
- A teleost CD46 is involved in the regulation of complement activation and pathogen infection.Scientific reports · 2017Article
- CsMAP34, a teleost MAP with dual role: A promoter of MASP-assisted complement activation and a regulator of immune cell activity.Scientific reports · 2016Article
- A Review of Functional Motifs Utilized by Viruses.Proteomes · 2016Review
- Article
- Ubiquitin-like Molecule ISG15 Acts as an Immune Adjuvant to Enhance Antigen-specific CD8 T-cell Tumor Immunity.Molecular therapy : the journal of the American Society of Gene Therapy · 2015Article
- Edwardsiella tarda MliC, a lysozyme inhibitor that participates in pathogenesis in a manner that parallels Ivy.Infection and immunity · 2015Article
- Insights into the antiviral immunity against grass carp (Ctenopharyngodon idella) reovirus (GCRV) in grass carp.Journal of immunology research · 2015Review
- ISG15 as a novel prognostic biomarker for hepatitis B virus-related hepatocellular carcinoma.International journal of clinical and experimental medicine · 2015Article
- Article
- The antiviral activities of ISG15.Journal of molecular biology · 2013Review
- Emerging roles for immunomodulatory functions of free ISG15.Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research · 2013Review
- Do reciprocal interactions between cell stress proteins and cytokines create a new intra-/extra-cellular signalling nexus?Cell stress & chaperones · 2013Article
- Zebrafish ISG15 exerts a strong antiviral activity against RNA and DNA viruses and regulates the interferon response.Journal of virology · 2013Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
ISG15 is an ubiquitin-like protein that is induced rapidly by interferon stimulation. Like ubiquitin, ISG15 forms covalent conjugates with its target proteins in a process called ISGylation, which in mammals is known to play a role in antiviral immunity. In contrast to mammalian ISG15, the function of teleost ISG15 is unclear. In this study, we identified and analyzed the function of an ISG15 homologue, CsISG15, from tongue sole (Cynoglossus semilaevis). CsISG15 is composed of 162 residues and possesses two tandem ubiquitin-like domains and the highly conserved LRGG motif found in all known ISG15. Expression of CsISG15 occurred in a wide range of tissues and was upregulated in kidney and spleen by viral and bacterial infection. In vitro study with primary head kidney (HK) lymphocytes showed that megalocytivirus infection caused induction of CsISG15 expression and extracellular release of CsISG15 protein. Purified recombinant CsISG15 (rCsISG15) activated HK macrophages and enhanced the expression of immune genes in HK lymphocytes, both these effects, however, were significantly reduced when the conserved LRGG sequence was mutated to LAAG. Further study showed that the presence of rCsISG15 during megalocytivirus infection of HK lymphocytes reduced intracellular viral load, whereas antibody blocking of CsISG15 enhanced viral infection. Likewise, interference with CsISG15 expression by RNAi promoted viral infection. Taken together, these results indicate that CsISG15, a teleost ISG15, promotes antiviral immune response and that, unlike mammalian ISG15, CsISG15 exerts its immunoregulatory effect in the form of an unconjugated extracellular cytokine. In addition, these results also suggest a role for the LRGG motif other than that in protein conjugation.
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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.