ArticleProceedings of the National Academy of Sciences of the United States of America2014
NLRX1 prevents mitochondrial induced apoptosis and enhances macrophage antiviral immunity by interacting with influenza virus PB1-F2 protein.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
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Who cites it
68 citing papers in PubMed, 114 citations in OpenAlex.
- Klebsiella pneumoniae inhibits vasodilation through capsule and T6SS-dependent pathways.Nature microbiology · 2026Article
- Decoding the lung-brain axis in influenza: from pulmonary infection to central nervous system injury.Journal of neuroinflammation · 2026Review
- Phenotypic CRISPR screens identify NLRX1 as an essential activator of the human mitochondrial permeability transition.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- The ELF3-TRIM22-MAVS signaling axis regulates type I interferon and antiviral responses.Journal of virology · 2025Article
- Comprehensive analysis of the succinylome in Vero cells infected with peste des petits ruminants virus Nigeria 75/1 vaccine strain.BMC veterinary research · 2025Article
- Pathogen-induced mitochondrial dysfunction: mechanistic insights, immune crosstalk, and therapeutic opportunities.Frontiers in cellular and infection microbiology · 2025Review
- Pattern Recognition by NOD-Like Receptors.Advances in experimental medicine and biology · 2025Review
- Mystery machine: the complex roles of NLRX1 in viral infection.Frontiers in immunology · 2025Review
- Influenza A Virus PB1-F2 Induces Affective Disorder by Interfering Synaptic Plasticity in Hippocampal Dentate Gyrus.Molecular neurobiology · 2024Article
- Pregnancy enhances antiviral immunity independent of type I IFN but dependent on IL-17-producing γδScience advances · 2024Article
- Lysophosphatidylcholines Promote Influenza Virus Reproduction through the MAPK/JNK Pathway in PMA-Differentiated THP-1 Macrophages.International journal of molecular sciences · 2024Article
- Article
- Triggering Degradation of Host Cellular Proteins for Robust Propagation of Influenza Viruses.International journal of molecular sciences · 2024Review
- Interaction among inflammasome, PANoptosise, and innate immune cells in infection of influenza virus: Updated review.Immunity, inflammation and disease · 2023Review
- Altered Respiratory Microbiomes, Plasma Metabolites, and Immune Responses in Influenza A Virus and Methicillin-Resistant Staphylococcus aureus Coinfection.Microbiology spectrum · 2023Article
- NLRX1 knockdown attenuates pro-apoptotic signaling and cell death in pulmonary hyperoxic acute injury.Scientific reports · 2023Article
- FBXO6 regulates the antiviral immune responses via mediating alveolar macrophages survival.Journal of medical virology · 2023Article
- Immunometabolic rewiring of tubular epithelial cells in kidney disease.Nature reviews. Nephrology · 2022Review
- Article
- Lung Fibrosis and Fibrosis in the Lungs: Is It All about Myofibroblasts?Biomedicines · 2022Review
8 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
To subvert host immunity, influenza A virus (IAV) induces early apoptosis in innate immune cells by disrupting mitochondria membrane potential via its polymerase basic protein 1-frame 2 (PB1-F2) accessory protein. Whether immune cells have mechanisms to counteract PB1-F2-mediated apoptosis is currently unknown. Herein, we define that the host mitochondrial protein nucleotide-binding oligomerization domain-like receptor (NLR)X1 binds to viral protein PB1-F2, preventing IAV-induced macrophage apoptosis and promoting both macrophage survival and type I IFN signaling. We initially observed that Nlrx1-deficient mice infected with IAV exhibited increased pulmonary viral replication, as well as enhanced inflammatory-associated pulmonary dysfunction and morbidity. Analysis of the lungs of IAV-infected mice revealed markedly enhanced leukocyte recruitment but impaired production of type I IFN in Nlrx1(-/-) mice. Impaired type I IFN production and enhanced viral replication was recapitulated in Nlrx1(-/-) macrophages and was associated with increased mitochondrial mediated apoptosis. Through gain- and loss-of-function strategies for protein interaction, we identified that NLRX1 directly bound PB1-F2 in the mitochondria of macrophages. Using a recombinant virus lacking PB1-F2, we confirmed that deletion of PB1-F2 abrogated NLRX1-dependent macrophage type I IFN production and apoptosis. Thus, our results demonstrate that NLRX1 acts as a mitochondrial sentinel protecting macrophages from PB1-F2-induced apoptosis and preserving their antiviral function. We further propose that NLRX1 is critical for macrophage immunity against IAV infection by sensing the extent of viral replication and maintaining a protective balance between antiviral immunity and excessive inflammation within the lungs.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.