The ELF3-TRIM22-MAVS signaling axis regulates type I interferon and antiviral responses

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

Published: March 31, 2025

ABSTRACT Activation of the innate immune response is essential for host cells to restrict dissemination invading viruses and other pathogens. Proteins belonging tripartite motif (TRIM) family are key effectors in antiviral immunity. Among these, TRIM22, a RING-type E3 ubiquitin ligase, has been recognized as significant regulator pathogenesis various diseases. In present study, we identified TRIM22 critical modulator mitochondrial signaling protein (MAVS) activation. Loss function led reduced production type I interferons (IFNs) viral infection such influenza A virus (IAV) or vesicular stomatitis (VSV), thereby facilitating replication. Mechanistically, was found enhance retinoic acid-inducible gene (RIG-I)-mediated through catalysis Lys63-linked polyubiquitination MAVS, which, turn, activated TANK-binding kinase 1 (TBK1)/interferon regulatory factor 3 (IRF3) pathway, driving IFN-β production. Additionally, shown inhibit assembly MAVS-NLRX1 inhibitory complex, further amplifying responses. Our findings also demonstrated that RNA upregulated expression via nuclear translocation ELF3, transcription activates expression. This loop underscores role modulating IFN providing insights into host’s defense mechanisms. research highlights potential targeting ELF3-TRIM22-MAVS axis therapeutic strategy enhancing immunity preventing infections. IMPORTANCE Interferon (IFN)-mediated responses crucial against foreign pathogens regulated by pathways. The family, its multifaceted roles regulation defense, plays part this process. our explored important helped regulate We enhances (MAVS), which producing interferons. Interestingly, discovered increases after an infection, due moved nucleus activate transcription. created feedback strengthens pathway. By uncovering these mechanisms, aimed understanding how system works provide could lead innovative therapies.

Language: Английский

Proteomic Profiling of COVID-19 Patients Sera: Differential Expression with Varying Disease Stage and Potential Biomarkers

Diagnostics, Journal Year: 2024, Volume and Issue: 14(22), P. 2533 - 2533

Published: Nov. 13, 2024

Background/Objectives: SARS-CoV-2 is one of the viruses that caused worldwide health issues. This effect mainly due to wide range disease prognoses it can cause. The aim this study determine protein profiles be used as potential biomarkers for patients’ stratification, well targets drug development. Methods: Eighty peripheral blood samples were collected from heathy patients admitted at a major tertiary care center in Riyadh, Saudi Arabia. A label-free quantitative mass spectrometry-based proteomic analysis was conducted on extracted sera. Protein–protein interactions and functional annotations identified proteins performed using STRING. Results: In total, two-hundred-eighty-eight dysregulated among all four categories. Dysregulated involved network map SARS-CoV-2, immune responses, complement activation, lipid transport. Compared healthy subjects, most common upregulated three categories CRP, LGALS3BP, SAA2, others pathways such ZAP70 IGLL1. Notably, we found fifteen significantly discriminate between healthy/recovered subjects moderate/under medication patients, which are SERPINA7, HSPD1 TTC41P proteins. These also downregulated under versus moderate patients. Conclusions: Our results emphasize possible association specific with pathogenesis their use targets. gave insights about likely increased upon infection but restored post recovery.

Language: Английский