scholarly journals E3 Ubiquitin Ligase RNF114 Inhibits Innate Immune Response to Red-Spotted Grouper Nervous Necrosis Virus Infection in Sea Perch by Targeting MAVS and TRAF3 to Mediate Their Degradation

2020 ◽  
Vol 206 (1) ◽  
pp. 77-88
Author(s):  
Yangxi Xiang ◽  
Wanwan Zhang ◽  
Peng Jia ◽  
Xiaobing Lu ◽  
Wei Liu ◽  
...  
Keyword(s):  
Immune Response ◽  
Virus Infection ◽  
Innate Immune Response ◽  
Ubiquitin Ligase ◽  
E3 Ubiquitin Ligase ◽  
Innate Immune ◽  
Nervous Necrosis Virus ◽  
Necrosis Virus ◽  
Sea Perch

scholarly journals The E3 ubiquitin ligase RNF185 facilitates the cGAS-mediated innate immune response

2017 ◽  
Vol 13 (3) ◽  
pp. e1006264 ◽  
Author(s):  
Qiang Wang ◽  
Liyuan Huang ◽  
Ze Hong ◽  
Zhongshi Lv ◽  
Zhaomin Mao ◽  
...  
Keyword(s):  
Immune Response ◽  
Innate Immune Response ◽  
Ubiquitin Ligase ◽  
E3 Ubiquitin Ligase ◽  
Innate Immune

scholarly journals An aberrantly sustained emergency granulopoiesis response accelerates postchemotherapy relapse in MLL1-rearranged acute myeloid leukemia in mice

2020 ◽  
Vol 295 (28) ◽  
pp. 9663-9675
Author(s):  
Hao Wang ◽  
Chirag A. Shah ◽  
Liping Hu ◽  
Weiqi Huang ◽  
Leonidas C. Platanias ◽  
...  
Keyword(s):  
Immune Response ◽  
Acute Myeloid Leukemia ◽  
Innate Immune Response ◽  
Ubiquitin Ligase ◽  
Myeloid Leukemia ◽  
Physiological Stress ◽  
E3 Ubiquitin Ligase ◽  
Innate Immune ◽  
Rtk Signaling ◽  
Acute Myeloid

Acute myeloid leukemia (AML) with mixed lineage leukemia 1 (MLL1) gene rearrangement is characterized by increased expression of a set of homeodomain transcription factors, including homeobox A9 (HOXA9) and HOXA10. The target genes for these regulators include fibroblast growth factor 2 (FGF2) and Ariadne RBR E3 ubiquitin ligase 2 (ARIH2). FGF2 induces leukemia stem cell expansion in MLL1-rearranged AML. ARIH2 encodes TRIAD1, an E3 ubiquitin ligase required for termination of emergency granulopoiesis and leukemia suppressor function in MLL1-rearranged AML. Receptor tyrosine kinases (RTKs), including the FGF receptor, are TRIAD1 substrates that are possibly relevant to these activities. Using transcriptome analysis, we found increased activity of innate immune response pathways and RTK signaling in bone marrow progenitors from mice with MLL1-rearranged AML. We hypothesized that sustained RTK signaling, because of decreased TRIAD1 activity, impairs termination of emergency granulopoiesis during the innate immune response and contributes to leukemogenesis in this AML subtype. Consistent with this, we found aberrantly sustained emergency granulopoiesis in a murine model of MLL1-rearranged AML, associated with accelerated leukemogenesis. Treating these mice with an inhibitor of TRIAD1-substrate RTKs terminated emergency granulopoiesis, delayed leukemogenesis during emergency granulopoiesis, and normalized innate immune responses when combined with chemotherapy. Emergency granulopoiesis also hastened postchemotherapy relapse in mice with MLL1-rearranged AML, but remission was sustained by ongoing RTK inhibition. Our findings suggest that the physiological stress of infectious challenges may drive AML progression in molecularly defined subsets and identify RTK inhibition as a potential therapeutic approach to counteract this process.

scholarly journals The E3 ubiquitin ligase TRIM21 negatively regulates the innate immune response to intracellular double-stranded DNA

2012 ◽  
Vol 14 (2) ◽  
pp. 172-178 ◽  
Author(s):  
Zhiqiang Zhang ◽  
Musheng Bao ◽  
Ning Lu ◽  
Leiyun Weng ◽  
Bin Yuan ◽  
...  
Keyword(s):  
Immune Response ◽  
Innate Immune Response ◽  
Ubiquitin Ligase ◽  
E3 Ubiquitin Ligase ◽  
Innate Immune ◽  
Double Stranded Dna

scholarly journals TRIM25 inhibits Influenza A infection by destabilising its mRNA and is redundant for the RIG-I pathway.

2021 ◽  
Author(s):  
Nila Roy Choudhury ◽  
Gregory Heikel ◽  
Ivan Trus ◽  
Rute Maria Dos Santos Pinto ◽  
Maryia Trubitsyna ◽  
...  
Keyword(s):  
Immune Response ◽  
Innate Immune Response ◽  
Ubiquitin Ligase ◽  
Influenza A ◽  
Rna Binding ◽  
Cultured Cells ◽  
Rna Viruses ◽  
E3 Ubiquitin Ligase ◽  
Innate Immune

The E3 ubiquitin ligase TRIM25 is a key factor in the innate immune response to RNA viruses. TRIM25 has been shown to play a role in the retinoic-acid-inducible gene-1 (RIG-I) pathway, which triggers expression of type 1 interferons upon viral infection. We and others have recently shown that TRIM25 is an RNA-binding protein, however not much is known about the RNA-binding roles of TRIM25 in the innate immune response to RNA viruses. Here, we demonstrate that influenza A virus (IAV A/PR/8/34_NS1(R38K41A)) infection is inhibited by TRIM25. Surprisingly, host RNA-binding deficient mutant TRIM25ΔRBD and TRIM25ΔRING, which lack E3 ubiquitin ligase activity rescued IAV inhibition in TRIM25 knock-out cells. Furthermore, we show that in human cultured cells activation of the RIG-I/interferon type 1 pathway mediated by an IAV-derived 5′-triphosphate RNA does not require TRIM25 activity. Additionally, knocking out TRIM25 does not affect the activity of the IAV polymerase. We present new evidence that TRIM25 restricts IAV by directly binding to and destabilising its mRNAs. Finally, we show that direct tethering of TRIM25 to RNA is sufficient to downregulate the targeted RNA. In summary, our results uncover a novel mechanism that TRIM25 uses to inhibit IAV infection and regulate RNA metabolism.

scholarly journals Mammalian Orthoreovirus Factories Modulate Stress Granule Protein Localization by Interaction with G3BP1

2017 ◽  
Vol 91 (21) ◽  
Author(s):  
Promisree Choudhury ◽  
Luke D. Bussiere ◽  
Cathy L. Miller
Keyword(s):  
Immune Response ◽  
Virus Infection ◽  
Innate Immune Response ◽  
Nonstructural Protein ◽  
Innate Immune ◽  
Common Mechanism ◽  
Effector Protein ◽  
Associated Proteins ◽  
Mammalian Orthoreovirus ◽  
Late Stages

ABSTRACT Mammalian orthoreovirus (MRV) infection induces phosphorylation of translation initiation factor eIF2α, which promotes the formation of discrete cytoplasmic inclusions, termed stress granules (SGs). SGs are emerging as a component of the innate immune response to virus infection, and modulation of SG assembly is a common mechanism employed by viruses to counter this antiviral response. We previously showed that MRV infection induces SGs early and then interferes with SG formation as infection proceeds. In this work, we found that SG-associated proteins localized to the periphery of virus-encoded cytoplasmic structures, termed virus factories (VFs), where viral transcription, translation, and replication occur. The localization of SG proteins to VFs was dependent on polysome dissociation and occurred via association of the SG effector protein, Ras-GAP SH3-binding protein 1 (G3BP1), with the MRV nonstructural protein σNS, which localizes to VFs via association with VF nucleating protein, μNS. Deletion analysis of the σNS RNA binding domain and G3BP1 RNA (RRM) and ribosomal (RGG) binding domains showed that σNS association and VF localization phenotypes of G3BP1 do not occur solely through RNA or ribosomal binding but require both the RRM and RGG domains of G3BP1 for maximal viral-factory-like structure (VFL) localization and σNS association. Coexpression of σNS and μNS resulted in disruption of normal SG puncta, and in cells lacking G3BP1, MRV replication was enhanced in a manner correlating with strain-dependent induction of host translation shutoff. These results suggest that σNS association with G3BP1 and relocalization of G3BP1 to the VF periphery play roles in SG disruption to facilitate MRV replication in the host translational shutoff environment. IMPORTANCE SGs and SG effector proteins have emerged as important, yet poorly understood, players in the host's innate immune response to virus infection. MRV infection induces SGs early during infection that are dispersed and/or prevented from forming during late stages of infection despite continued activation of the eIF2α signaling pathway. Cellular and viral components involved in disruption of SGs during late stages of MRV infection remain to be elucidated. This work provides evidence that MRV disruption of SGs may be facilitated by association of the MRV nonstructural protein σNS with the major SG effector protein G3BP1 and subsequent localization of G3BP1 and other SG-associated proteins around the peripheries of virus-encoded factories, interrupting the normal formation of SGs. Our findings also reveal the importance of G3BP1 as an inhibitor of MRV replication during infection for the first time.

scholarly journals Innate immune response to encephalomyocarditis virus infection mediated by CD1d

Immunology ◽  
2003 ◽  
Vol 110 (4) ◽  
pp. 519-526 ◽  
Author(s):  
Mark A. Exley ◽  
Nancy J. Bigley ◽  
Olivia Cheng ◽  
Angela Shaulov ◽  
Syed Muhammad Ali Tahir ◽  
...  
Keyword(s):  
Immune Response ◽  
Virus Infection ◽  
Innate Immune Response ◽  
Innate Immune ◽  
Encephalomyocarditis Virus
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