{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:18:59Z","timestamp":1787026739633,"version":"build-2736575974"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,7,29]],"date-time":"2021-07-29T00:00:00Z","timestamp":1627516800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:p>\n                    Type I interferons (IFN), a family of cytokines widely expressed in various tissues, play important roles in anti-infection immunity. Nevertheless, it is not known whether\n                    <jats:italic>Brucella<\/jats:italic>\n                    spp. could interfere with IFN-I production induced by other pathogens. This study investigated the regulatory roles of\n                    <jats:italic>Brucella<\/jats:italic>\n                    outer membrane protein (Omp)25 on the IFN-I signaling pathway and found that Omp25 inhibited the production of IFN-\u03b2 and its downstream IFN-stimulated genes induced by various DNA viruses or IFN-stimulatory DNA in human, murine, porcine, bovine, and ovine monocyte\/macrophages or peripheral blood mononuclear cells.\n                    <jats:italic>Brucella<\/jats:italic>\n                    Omp25 suppressed the phosphorylation of stimulator of IFN genes (STINGs) and IFN regulatory factor 3 and nuclear translocation of phosphorylated IFN regulatory factor 3 in pseudorabies virus- or herpes simplex virus-1-infected murine, human, or porcine macrophages. Furthermore, we found that\n                    <jats:italic>Brucella<\/jats:italic>\n                    Omp25 promoted cyclic guanosine monophosphate\u2013adenosine monophosphate synthase (cGAS) degradation\n                    <jats:italic>via<\/jats:italic>\n                    the proteasome-dependent pathway, resulting in a decreased cyclic guanosine monophosphate\u2013adenosine monophosphate production and downstream signaling activation upon DNA virus infection or IFN-stimulatory DNA stimulation. Mapping the predominant function domain of Omp25 showed that the amino acids 161 to 184 of Omp25 were required for Omp25-induced cGAS degradation, among which five amino acid residues (R176, Y179, R180, Y181, and Y184) were required for the inhibitory effect of Omp25 on IFN-\u03b2 induction. Altogether, our results demonstrated that\n                    <jats:italic>Brucella<\/jats:italic>\n                    Omp25 inhibits cGAS STING signaling pathway-induced IFN-\u03b2\n                    <jats:italic>via<\/jats:italic>\n                    facilitating the ubiquitin\u2013proteasome-dependent degradation of cGAS in various mammalian monocyte\/macrophages.\n                  <\/jats:p>","DOI":"10.3389\/fmicb.2021.702881","type":"journal-article","created":{"date-parts":[[2021,7,29]],"date-time":"2021-07-29T06:52:17Z","timestamp":1627541537000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":13,"title":["Brucella spp. Omp25 Promotes Proteasome-Mediated cGAS Degradation to Attenuate IFN-\u03b2 Production"],"prefix":"10.3389","volume":"12","author":[{"given":"Ruizhen","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenli","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangrui","family":"Yin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangfang","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenyu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingchen","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohua","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Du","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dewen","family":"Tong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,7,29]]},"reference":[{"key":"B1","doi-asserted-by":"crossref","first-page":"17037","DOI":"10.1038\/nmicrobiol.2017.37","article-title":"Dengue virus NS2B protein targets cGAS for degradation and prevents mitochondrial DNA sensing during infection.","volume":"2","author":"Aguirre","year":"2017","journal-title":"Nat. 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