% IMPORTANT: The following is UTF-8 encoded. This means that in the presence % of non-ASCII characters, it will not work with BibTeX 0.99 or older. % Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or % “biber”. @ARTICLE{Acharya:278654, author = {Acharya, Dhiraj and Sayyad, Zuberwasim and Hoenigsperger, Helene and Hirschenberger, Maximilian and Zurenski, Matthew and Balakrishnan, Kannan and Zhu, Junji and Gableske, Sebastian and Kato, Jiro and Zhang, Shen-Ying and Casanova, Jean-Laurent and Moss, Joel and Sparrer, Konstantin M J and Gack, Michaela U}, title = {{TRIM}23 mediates c{GAS}-induced autophagy in anti-{HSV} defense.}, journal = {Nature Communications}, volume = {16}, number = {1}, issn = {2041-1723}, address = {[London]}, publisher = {Springer Nature}, reportid = {DZNE-2025-00610}, pages = {4418}, year = {2025}, abstract = {The cGAS-STING pathway, well-known to elicit interferon (IFN) responses, is also a key inducer of autophagy upon virus infection or other stimuli. Whereas the mediators for cGAS-induced IFN responses are well characterized, much less is known about how cGAS elicits autophagy. Here, we report that TRIM23, a unique TRIM protein harboring both ubiquitin E3 ligase and GTPase activity, is crucial for cGAS-STING-dependent antiviral autophagy. Genetic ablation of TRIM23 impairs autophagic control of HSV-1 infection. HSV-1 infection or cGAS-STING stimulation induces TBK1-mediated TRIM23 phosphorylation at S39, which triggers TRIM23 autoubiquitination and GTPase activity and ultimately elicits autophagy. Fibroblasts from a patient with herpes simplex encephalitis heterozygous for a dominant-negative, kinase-inactivating TBK1 mutation fail to activate autophagy by TRIM23 and cGAS-STING. Our results thus identify the cGAS-STING-TBK1-TRIM23 axis as a key autophagy defense pathway and may stimulate new therapeutic interventions for viral or inflammatory diseases.}, keywords = {Autophagy: immunology / Humans / Nucleotidyltransferases: metabolism / Nucleotidyltransferases: genetics / Nucleotidyltransferases: immunology / Herpesvirus 1, Human: immunology / Herpesvirus 1, Human: physiology / Protein Serine-Threonine Kinases: metabolism / Protein Serine-Threonine Kinases: genetics / Membrane Proteins: metabolism / Membrane Proteins: genetics / Animals / Phosphorylation / Fibroblasts: metabolism / Fibroblasts: virology / Mice / Ubiquitin-Protein Ligases: metabolism / Ubiquitin-Protein Ligases: genetics / Herpes Simplex: immunology / Herpes Simplex: virology / HEK293 Cells / Signal Transduction / Ubiquitination / Nucleotidyltransferases (NLM Chemicals) / Protein Serine-Threonine Kinases (NLM Chemicals) / Membrane Proteins (NLM Chemicals) / cGAS protein, human (NLM Chemicals) / TBK1 protein, human (NLM Chemicals) / STING1 protein, human (NLM Chemicals) / Ubiquitin-Protein Ligases (NLM Chemicals) / cGAS protein, mouse (NLM Chemicals)}, cin = {AG Sparrer}, ddc = {500}, cid = {I:(DE-2719)1910003}, pnm = {351 - Brain Function (POF4-351)}, pid = {G:(DE-HGF)POF4-351}, typ = {PUB:(DE-HGF)16}, pubmed = {pmid:40360474}, pmc = {pmc:PMC12075517}, doi = {10.1038/s41467-025-59338-5}, url = {https://pub.dzne.de/record/278654}, }