MAVS positively regulates mitochondrial integrity and metabolic fitness in antigen receptor-activated B cells
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA949650 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR23997117_1.fastq.gz | Fastqsanger.gz | |||
| SRR23997117_2.fastq.gz | Fastqsanger.gz | |||
| SRR23997118_1.fastq.gz | Fastqsanger.gz | |||
| SRR23997118_2.fastq.gz | Fastqsanger.gz | |||
| SRR23997119_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 36 |
Similar Datasets
Project description:The role of mitochondrial homeostatic control in the metabolic remodeling associated with antigen receptor stimulation in B cells remains incompletely defined. Here we report that the mitochondrial antiviral signaling (MAVS) adaptor protein is involved in B cell receptor (BCR) initiated cellular proliferation and prolonged survival. MAVS is well known as a mitochondrial tethered signaling adaptor for sensing viral double-stranded RNA and type I interferon inducer. The role of MAVS downstream of BCR stimulation was recognized in absence of interferon, suggesting a new pathway for MAVS activation that is independent of viral infection. Mitochondria of BCR-activated MAVS-deficient B cells exhibited a damaged phenotype including disrupted mitochondrial morphology, excess mitophagy and the temporal progressive blunting of mitochondrial oxidative capacity with mitochondrial hyperpolarization and cell death. Co-stimulation with anti-CD40, in addition to BCR stimulation, corrected the proliferative gap between MAVS-deficient and -sufficient B cells; however, mitochondrial structural defects and functionality were only partially restored. Our data reveal a previously unrecognized role of MAVS in controlling mitochondrial homeostasis in response to BCR initiated B cell proliferation.
2023-07-26 | GSE228413 | GEO
Project description:Viruses target mitochondria, critical for antiviral defense and metabolism, to evade immunity. While mitochondrial antiviral-signaling protein (MAVS) is known for its regulation of type I interferon (IFN) signaling, we discover that its overarching primary role is safeguarding mitochondrial integrity against virus- and toxin-induced mitophagy. This function is critical in enacting a potent, IFN/NF-κB-independent antiviral response. Using SARS-CoV-2 (CoV-2) infection model, where disruption of MAVS aggregation and induction of mitophagy were observed, we demonstrate that functional MAVS prevents CoV-2-induced mitophagy and restricts viral replication without engaging type I or III interferon (IFN), and NF-κB pathways. Employing MAVS-knockout and MAVS:IFNAR1 double-knockout cells, and inhibition studies, our results further establish MAVS as a critical protector against virus- and chemical mitotoxin-induced mitophagy. Loss of MAVS results in increased mitochondrial membrane depolarization, reduced oxidative potential, and increased PINK1-dependent mitophagy leading to elevated viral replication-all reversed by MAVS supplementation. The IFN-independent antiviral immunity generated by MAVS-driven mitochondrial safeguarding conferred robust protection against mitophagy-inducing viruses, such as CoV-2 and JEV, but not DENV, which does not trigger mitophagy. By facilitating the mitochondrial integrity, MAVS governs the overall innate antiviral immunity- integrating IFN-dependent and IFN-independent mechanisms- and energy metabolism in the host cells. Thus, the regulation of these central functions makes MAVS a prime target for subverting host defenses and cellular energy homeostasis. These insights underscoring MAVS’s wider role in sustaining mitochondrial homeostasis positions it as a promising target for antiviral strategies.
2025-04-30 | GSE293066 | GEO
Project description:Activated B cells experience metabolic changes that require mitochondrial remodeling, in a process incompletely defined. In this study, we report that mitochondrial antiviral signaling protein (MAVS) is involved in BCR-initiated cellular proliferation and prolonged survival. MAVS is well known as a mitochondrial-tethered signaling adaptor with a central role in viral RNA-sensing pathways that induce type I IFN. The role of MAVS downstream of BCR stimulation was recognized in absence of IFN, indicative of a path for MAVS activation that is independent of viral infection. Mitochondria of BCR-activated MAVS-deficient mouse B cells exhibited a damaged phenotype including disrupted mitochondrial morphology, excess mitophagy, and the temporal progressive blunting of mitochondrial oxidative capacity with mitochondrial hyperpolarization and cell death. Costimulation of MAVS-deficient B cells with anti-CD40, in addition to BCR stimulation, partially corrected the mitochondrial structural defects and functionality. Our data reveal a (to our knowledge) previously unrecognized role of MAVS in controlling the metabolic fitness of B cells, most noticeable in the absence of costimulatory help.
| S-EPMC10587501 | biostudies-literature
Project description:MAVS Orchestrates a Potent IFN-independent Antiviral Immunity by 2 Preserving Mitochondrial Integrity
| PRJNA1242734 | ENA
Project description:We found that fuse ΔLMP1 to MAVS could strengthen MAVS mediated inhibition of PRRSV replication in MARC-145 cells. To better understand the biological function of the fusion protein ΔLMP1-MAVS, overall gene expression of MARC-145 cells transfected with ΔLMP1-MAVS or MAVS was evaluated by mRNA-seq. The result showed that ΔLMP1-MAVS upregulated a number of genes associated with innate immune responses to viral infection, including plenty of interferon-stimulated genes. This study provides reference date to research the working mechanism of ΔLMP1-MAVS.
2019-03-05 | GSE111530 | GEO
Project description:Immune signaling needs to be well-regulated to promote clearance of pathogens, while preventing aberrant inflammation. Interferons (IFNs) and antiviral genes are activated by the detection of viral RNA by RIG-I-like receptors (RLRs). Signal transduction downstream of RLRs proceeds through a multiprotein complex organized around the central adaptor protein MAVS. While protein-protein interactions and post-translational modifications are critical for the formation of the MAVS signalosome, whether RNA play a role in organizing these platforms is largely unknown. RNA can modulate protein complex function by allosteric regulation or by serving as a molecular guide or scaffold. We have found that MAVS directly interacts with the 3’ untranslated regions of cellular mRNAs through its central intrinsically disordered domain. Eliminating RNA by RNase treatment disrupts the MAVS signalosome and inhibits phosphorylation of the transcription factor IRF3. These findings support the hypothesis that RNA molecules scaffold the MAVS signaling platform to induce IFNs. Indeed, RNase treatment alters interactions between MAVS and newly identified regulators of RLR signaling. Together, this work uncovers a function for cellular RNA in promoting signaling through MAVS and highlights a generalizable principle of RNA regulatory control of cytoplasmic immune signaling complexes.
2025-03-19 | GSE244000 | GEO
Project description:This modification plays a critical role in regulating protein function and cellular processes.MAVS succination sites were identified using mass spectrometry (MS). Identify succination sites of human MAVS protein.
2025-05-26 | PXD061060 | Pride
Project description:Innate immunity serves as the primary defense against viral and microbial infections in humans. Among its components, retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) are well-characterized intracellular pattern-recognition proteins that trigger innate immune responses upon viral infection. However, the precise influence of cellular metabolites, especially fatty acids, on the regulation of RLR-mediated antiviral innate immunity remains largely elusive. Here, through screening a metabolite library, palmitic acid (PA) has been identified as a crucial metabolite responsible for modulating antiviral infections. Mechanistically, PA induces the palmitoylation of MAVS, leading to MAVS aggregation and subsequent activation, thereby enhancing the innate immune response against viral infections. Functionally, the enzyme palmitoyl-transferase ZDHHC24 plays a key role in catalyzing the palmitoylation of MAVS at both C46 and C79 residues, thereby facilitating the transduction of RLR-mediated TBK1-IRF3-IFN signaling pathway, particularly under conditions of PA stimulation or high-fat diet feeding. Conversely, the absence of ZDHHC24 significantly attenuates virus-induced innate immune responses in both cells and mice. Moreover, APT2 counteracts with ZDHHC24 to de-palmitoylate MAVS, thus inhibiting the antiviral response. Consequently, inhibition of APT2 using compounds like ML349 effectively reverses MAVS palmitoylation and activation in response to antiviral infections. These findings underscore the critical role of PA and ZDHHC24 in regulating antiviral innate immunity through MAVS palmitoylation, and suggest potential therapeutic strategies for combating viral infections, such as enhancing PA intake or specifically targeting APT2.
2024-09-10 | PXD054077 | Pride
Project description:Neurotropic viruses like vesicular stomatitis virus (VSV) can infect the central nervous system (CNS) through the olfactory route. Following intranasal instillation, VSV moves along the axons of olfactory sensory neurons to the olfactory bulb. While within the olfactory bulb the spread of the virus is controlled by microglia activation and the recruitment of peripheral leukocytes, some of the underlying mechanisms remain unknown. To investigate these mechanisms, we used mice with conditional deletions of the mitochondrial antiviral-signaling protein (MAVS), an adaptor for RIG-I-like receptor (RLR)-signaling. By selectively deleting MAVS in neurons, astrocytes, or long-lived myeloid cells, we discovered that RLR-signaling specifically within brain-resident myeloid cells is crucial for protection against the virus. Mice with a MAVS deletion in these myeloid cells showed normal myeloid cell and leukocyte infiltration into the brain. However, the P2RY12+ microglia showed aberrant expression of genes involved in antigen cross-presentation.Furthermore, flow cytometry experiments revealed diminished MHC class I expression on MAVS deficient microglia. Moreover, CNS-infiltrating CD8+T cells had dysfunctional transcriptional profiles. Therefore, our findings indicate that during viral CNS infection, MAVS signaling in brain-resident myeloid cells, presumably microglia, is essential for antigen cross-presentation and the relicensing of protective, infiltrating CD8+ T cells.
2025-07-07 | GSE301540 | GEO
Project description:MAVS-mediated cytosolic RNA sensing plays a central role in tumor immunogenicity. However, the effects of host MAVS signaling on antitumor immunity remains uncertain. Here, we demonstrate that host MAVS pathway drives accelerated tumor growth and impairs antitumor immunity, while MAVS knockout in dendritic cells (DCs) promotes tumor-reactive CD8+ T cell responses. Specifically, the CD8+ T cell priming capacity is enhanced by lack of functional MAVS in a type I interferon-independent, but IL-12-dependent, manner. Mechanistically, loss of RIG-I/MAVS cascade activates non-canonical NF-κB pathway and in turn induces IL-12 production by DCs, resulting in CD8+ T cell: DC crosstalk licensed by IFN-γ and IL-12. Moreover, ablation of host MAVS sensitizes tumors to immunotherapy and attenuates radiation resistance, thereby facilitating the maintenance of effector CD8+ T cells. These findings identify that host MAVS pathway acts as an immune checkpoint of DC-driven antitumor immunity, indicating the development of DC-based immunotherapies through MAVS signaling antagonism.
2023-08-15 | GSE236763 | GEO