Abstract
Innate immune detection of nucleic acids is important for initiation of antiviral responses. Detection of intracellular DNA activates STING-dependent type I interferons (IFNs) and the ASC-dependent inflammasome. Certain members of the AIM2-like receptor (ALR) gene family contribute to each of these pathways, but most ALRs remain uncharacterized. Here, we identify five novel murine ALRs and perform a phylogenetic analysis of mammalian ALRs, revealing a remarkable diversification of these receptors among mammals. We characterize the expression, localization, and functions of the murine and human ALRs and identify novel activators of STING-dependent IFNs and the ASC-dependent inflammasome. These findings validate ALRs as key activators of the antiviral response and provide an evolutionary and functional framework for understanding their roles in innate immunity.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Base Sequence
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Cells, Cultured
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DNA-Binding Proteins
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Embryo, Mammalian / cytology
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Evolution, Molecular*
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Fibroblasts / cytology
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Fibroblasts / metabolism
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Gene Expression
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Genetic Variation*
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HEK293 Cells
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HeLa Cells
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Humans
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Inflammasomes / metabolism
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Interferons / genetics
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Interferons / metabolism
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Mammals / genetics*
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Membrane Proteins / deficiency
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Membrane Proteins / genetics
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Membrane Proteins / metabolism
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Molecular Sequence Data
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Nuclear Proteins / classification
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Nuclear Proteins / genetics*
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Nuclear Proteins / metabolism
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Phosphoproteins / classification
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Phosphoproteins / genetics
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Phosphoproteins / metabolism
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Phylogeny
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RNA Interference
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Reverse Transcriptase Polymerase Chain Reaction
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Sequence Homology, Nucleic Acid
Substances
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Aim2 protein, mouse
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DNA-Binding Proteins
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Ifi16 protein, mouse
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Inflammasomes
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Membrane Proteins
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Nuclear Proteins
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Phosphoproteins
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Sting1 protein, mouse
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Interferons