The precise regulation of the innate immune response is essential for the maintenance of homeostasis. MAVS and STING play key roles in immune signaling pathways activated by RNA and DNA viruses, respectively. Here, we showed that DHCR24 impaired the antiviral response by targeting MAVS and STING. Notably, DHCR24 interacts with MAVS and STING and inhibits TRIM21-triggered K27-linked ubiquitination of MAVS and AMFR-triggered K27-linked ubiquitination of STING, restraining the activation of MAVS and STING, respectively. Together, this study elucidates how one cholesterol key enzyme orchestrates two antiviral signal transduction pathways.
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http://dx.doi.org/10.1128/jvi.01513-23 | DOI Listing |
Immunol Res
January 2025
, Auckland, New Zealand.
Cytotoxic DNAs, methylation, histones and histones binding proteins are speculated to induce DNA sensors. Under stressed condition, the antigenic patterns, PAMPs and DAMPs, trigger the hyperactive innate response through DNA, DNA-RNA hybrids, oligonucleotides, histones and mtDNA to initiate cGAMP-STING-IFN I cascade. HSV -1&2, HIV, Varicella- Zoster virus, Polyomavirus, Cytomegalovirus, and KSHV negatively regulate the STING-MAVS-TBK-1/1KKE pathway.
View Article and Find Full Text PDFSci Adv
January 2025
MRC Laboratory of Medical Sciences (LMS), Du Cane Road, London W12 0NN, UK.
Induction of senescence by chemotherapeutic agents arrests cancer cells and activates immune surveillance responses to contribute to therapy outcomes. In this investigation, we searched for ways to enhance the NK-mediated elimination of senescent cells. We used a staggered screen approach, first identifying siRNAs potentiating the secretion of immunomodulatory cytokines to later test for their ability to enhance NK-mediated killing of senescent cells.
View Article and Find Full Text PDFCrit Rev Oncol Hematol
December 2024
Wuxi Medical College, Jiangnan University, Wuxi 214122, China. Electronic address:
The mitochondrial antiviral signaling protein (MAVS) is a pivotal adaptor in the antiviral innate immune signaling pathway and plays a crucial role in the activation of antiviral defences. This comprehensive review delves into the multifaceted functions of MAVS, spanning from its integral role in the RIG-I-like receptor (RLR) pathway to its emerging roles in tumor biology and autoimmune diseases. We discuss the structural and functional aspects of MAVS, its activation mechanisms, and the intricate regulatory networks that govern its activity.
View Article and Find Full Text PDFInt J Biol Macromol
December 2024
Research Center of Avian Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China; International Joint Research Center for Animal Disease Prevention and Control of Sichuan Province, Chengdu 611130, China.; College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China; Key Laboratory of Animal Disease and Human Health of Sichuan Province, Chengdu 611130, China; Engineering Research Center of Southwest Animal Disease Prevention and Control Technology, Ministry of Education of the People's Republic of China, Chengdu 611130, China.
The picornavirus 3C protein plays a crucial role in viral infection. One of its functions is inhibiting the immune response by cleaving or degrading innate immune-related proteins to promote viral infection. Annexin A2 (ANXA2) is a multifunctional host protein that plays a key role in various cellular processes, it also participates in viral infection.
View Article and Find Full Text PDFEMBO J
December 2024
Institute of Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn, Bonn, Germany.
The cytosolic nucleic acid sensors RIG-I and cGAS induce type-I interferon (IFN)-mediated immune responses to RNA and DNA viruses, respectively. So far no connection between the two cytosolic pathways upstream of IKK-like kinase activation has been investigated. Here, we identify heterogeneous nuclear ribonucleoprotein M (hnRNPM) as a positive regulator of IRF3 phosphorylation and type-I IFN induction downstream of both cGAS and RIG-I.
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