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1000
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Abstract/Summary
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<jats:p>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 <jats:italic>Brucella</jats:italic> spp. could interfere with IFN-I production induced by other pathogens. This study investigated the regulatory roles of <jats:italic>Brucella</jats:italic> outer membrane protein (Omp)25 on the IFN-I signaling pathway and found that Omp25 inhibited the production of IFN-β 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. <jats:italic>Brucella</jats:italic> 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 <jats:italic>Brucella</jats:italic> Omp25 promoted cyclic guanosine monophosphate–adenosine monophosphate synthase (cGAS) degradation <jats:italic>via</jats:italic> the proteasome-dependent pathway, resulting in a decreased cyclic guanosine monophosphate–adenosine 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-β induction. Altogether, our results demonstrated that <jats:italic>Brucella</jats:italic> Omp25 inhibits cGAS STING signaling pathway-induced IFN-β <jats:italic>via</jats:italic> facilitating the ubiquitin–proteasome-dependent degradation of cGAS in various mammalian monocyte/macrophages.</jats:p>
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1000
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Hinweis
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DeepGreen-ID: fb1e2c9b31c84207885015aec1065cd1 ; metadata provieded by: DeepGreen (https://www.oa-deepgreen.de/api/v1/), LIVIVO search scope life sciences (http://z3950.zbmed.de:6210/livivo), Crossref Unified Resource API (https://api.crossref.org/swagger-ui/index.html), to.science.api (https://frl.publisso.de/), ZDB JSON-API (beta) (https://zeitschriftendatenbank.de/api/), lobid - Dateninfrastruktur für Bibliotheken (https://lobid.org/resources/search)
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