TRIM21/Ro52 - Roles in Innate Immunity and Autoimmune Disease

Frontiers in Immunology, Journal Year: 2021, Volume and Issue: 12

Published: Sept. 6, 2021

TRIM21 (Ro52/SSA1) is an E3 ubiquitin ligase with key roles in immune host defence, signal transduction, and possibly cell cycle regulation. It also autoantibody target Sjögren's syndrome, systemic lupus erythematosus, other rheumatic autoimmune diseases. Here, we summarise the structure function of this enzyme, its innate immunity, adaptive immunity cellular homeostasis, pathogenesis autoimmunity against TRIM21, potential impacts autoantibodies to intracellular protein.

Language: Английский

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Multiple Roles of TRIM21 in Virus Infection

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(2), P. 1683 - 1683

Published: Jan. 14, 2023

The tripartite motif protein 21 (TRIM21) belongs to the TRIM family, possessing an E3 ubiquitin ligase activity. Similar other TRIMs, TRIM21 also contains three domains (named RBCC), including Really Interesting New Gene (RING) domain, one or two B-Box (B-Box), and PRY/SPRY domain. Notably, we found that RING are relatively more conservative than suggesting of different species had similar functions. Recent results showed participates in virus infection by directly interacting with viral proteins modulating immune inflammatory responses. acts as a cytosol high-affinity antibody Fc receptor, binding antibody–virus complex triggering indirect antiviral antibody-dependent intracellular neutralization (ADIN). This paper focuses on recent progress mechanism during application prospects infection.

Language: Английский

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A Comprehensive View on the Protein Functions of Porcine Epidemic Diarrhea Virus

Genes, Journal Year: 2024, Volume and Issue: 15(2), P. 165 - 165

Published: Jan. 26, 2024

Porcine epidemic diarrhea (PED) virus (PEDV) is one of the main pathogens causing in piglets and fattening pigs. The clinical signs PED are vomiting, acute diarrhea, dehydration, mortality resulting significant economic losses becoming a major challenge pig industry. PEDV possesses various crucial structural functional proteins, which play important roles viral structure, infection, replication, assembly, release, as well escaping host innate immunity. Over past few years, there has been progress study pathogenesis, revealing role interaction between proteins cytokines infection. At present, control measure against vaccine immunization sows, but protective effect for emerging strains still insufficient, no ideal safe efficient vaccine. Although scientists have persistently delved their research into intricate structure functionalities genome pathogenic mechanism remains incompletely elucidated. Here, we focus on reviewing nonstructural to facilitate understanding biological processes such infection pathogenesis.

Language: Английский

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Genome-scale CRISPR screen identifies TRIM2 and SLC35A1 associated with porcine epidemic diarrhoea virus infection

International Journal of Biological Macromolecules, Journal Year: 2023, Volume and Issue: 250, P. 125962 - 125962

Published: July 25, 2023

Language: Английский

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OAS1 suppresses African swine fever virus replication by recruiting TRIM21 to degrade viral major capsid protein

Journal of Virology, Journal Year: 2023, Volume and Issue: 97(10)

Published: Oct. 10, 2023

African swine fever virus (ASFV) completes the replication process by resisting host antiviral response

Language: Английский

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ZCCHC3 inhibits PEDV proliferation by degrading nuclear coat proteins via the proteasome pathway

Veterinary Microbiology, Journal Year: 2025, Volume and Issue: 304, P. 110449 - 110449

Published: March 6, 2025

Language: Английский

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Host restriction factors against porcine epidemic diarrhea virus: a mini-review

Veterinary Research, Journal Year: 2025, Volume and Issue: 56(1)

Published: March 24, 2025

Abstract Porcine epidemic diarrhea is an acute contagious disease caused by porcine virus (PEDV), which severely constrains the development of global swine industry. Host restriction factors constitute a vital defensive barrier against viral infections, typically interacting with viruses at specific stages their replication process to disrupt it. Considering that traditional PEDV vaccines often struggle effectively activate mucosal immunity in sows and thereby fail provide reliable passive piglets via milk, this review focuses on host play crucial roles restricting infection replication. The aim identify potential targets for anti-PEDV drugs offer insights exploration novel vaccine adjuvants.

Language: Английский

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PTBP1 suppresses porcine epidemic diarrhea virus replication via inducing protein degradation and IFN production

Journal of Biological Chemistry, Journal Year: 2023, Volume and Issue: 299(8), P. 104987 - 104987

Published: June 29, 2023

Porcine epidemic diarrhea virus (PEDV) causes severe morbidity and mortality among newborn piglets. It significantly threatens the porcine industry in China around globe. To accelerate developmental pace of drugs or vaccines against PEDV, a deeper understanding interaction between viral proteins host factors is crucial. The RNA-binding protein, polypyrimidine tract-binding protein 1 (PTBP1), crucial for controlling RNA metabolism biological processes. present work focused on exploring effect PTBP1 PEDV replication. was upregulated during infection. nucleocapsid (N) degraded through autophagic proteasomal degradation pathways. Moreover, recruits MARCH8 (an E3 ubiquitin ligase) NDP52 (a cargo receptor) N catalysis selective autophagy. Furthermore, induces innate antiviral response via upregulating expression MyD88, which then regulates TRAF3/TRAF6 phosphorylation TBK1 IRF3. These processes activate typeⅠIFN signaling pathway to antagonize Collectively, this illustrates new mechanism related PTBP1-induced restriction, where degrades production suppress

Language: Английский

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Ubiquitin-dependent proteasomal degradation of small hepatitis B virus surface antigen mediated by TRIM21 and antagonized by OTUD4

Journal of Virology, Journal Year: 2025, Volume and Issue: unknown

Published: April 25, 2025

ABSTRACT The small hepatitis B surface antigen (SHBs) is the most abundant virus (HBV) protein in individuals infected with HBV, and clearance of HBV antigen, which primarily composed SHBs, considered a surrogate biomarker for achieving functional cure chronic HBV. Understanding SHBs degradation crucial its elimination targeted eradication strategies. This study demonstrates that undergoes via ubiquitin/proteasome pathway, through K48-linked ubiquitination, K122 as critical ubiquitination site. Utilizing immunoprecipitation mass spectrometry, we identified TRIM21 (an E3 ubiquitin ligase) OTUD4 (a deubiquitinase) key regulators SHBs. We verified direct interaction between TRIM21’s coiled-coil domain, well N-terminal amino acids 1–180 OTUD4, using coimmunoprecipitation glutathione S-transferase (GST) pull-down assays both vivo vitro settings. was observed to reduce stability abundance by promoting polyubiquitination, whereas acted negate effects TRIM21-induced thereby stabilizing increasing levels Notably, TRIM21-mediated substantially impaired subviral particle virion production biological activities such migratory angiogenic capabilities, opposite effect produced introduction OTUD4. These findings suggest modulate function ubiquitination-dependent proteasomal offering new insights into clearing intervening progression HBV-related liver diseases. IMPORTANCE structural component particles infection. Gaining better understanding pathways may help inform strategies potentially support design therapies. However, specific mechanisms processes involved remain largely unexplored. reveals degraded specifically at promotes enhancing while stabilizes counteracting effects. reduces stability, production, related activities, accumulation. highlight roles regulating function, potential interventions

Language: Английский

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Interleukin 27, Similar to Interferons, Modulates Gene Expression of Tripartite Motif (TRIM) Family Members and Interferes with Mayaro Virus Replication in Human Macrophages

Viruses, Journal Year: 2024, Volume and Issue: 16(6), P. 996 - 996

Published: June 20, 2024

Background: The Tripartite motif (TRIM) family includes more than 80 distinct human genes. Their function has been implicated in regulating important cellular processes, including intracellular signaling, transcription, autophagy, and innate immunity. During viral infections, macrophages are key components of immunity that produce interferons (IFNs) IL27. We recently published IL27 IFNs induce transcriptional changes various genes, those involved JAK-STAT signaling. Furthermore, share proinflammatory antiviral pathways monocyte-derived (MDMs), resulting both common unique expression inflammatory factors IFN-stimulated genes (ISGs) encoding proteins. Interestingly, many TRIM proteins have recognized as ISGs recent years. Although it is already very well described induced by IFNs, not fully understood whether Therefore, this study, we examined the effect stimulation with type I, II, III on mRNA profiles MDMs. Methods: used bulk RNA-seq to examine profile MDMs treated or Initially, characterized patterns different subfamilies using a heatmap. Subsequently, volcano plot was employed identify commonly differentially expressed Additionally, conducted gene ontology analysis ClueGO explore biological processes regulated TRIMs, created gene-gene interaction network GeneMANIA, protein-protein interactions STRING database. Finally, data validated RT-qPCR. Mayaro virus replication also evaluated. Results: found IL27, similar upregulates several genes’ macrophages. Specifically, identified three (TRIM19, 21, 22) all types IFNs. performed first report regulation TRIM19, 22, 69 response TRIMs broad range defense viruses, life cycle regulation, negative processes. In addition, observed decrease previously Conclusions: Our results show like modulates TRIM-family members induction an response. functional demonstrated that, IFN, reduced This implies similarities at level. Moreover, identifying groups their differential expressions provides new insights into regulatory mechanisms underlying

Language: Английский

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