{"id":48857,"date":"2025-11-16T00:46:08","date_gmt":"2025-11-15T23:46:08","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2025\/11\/16\/grass-carp-ctenopharyngodon-idella-smyd3-negatively-regulates-antiviral-innate-immunity-by-methylating-irf3-and-irf7-during-gcrv-infection\/"},"modified":"2025-11-16T00:46:08","modified_gmt":"2025-11-15T23:46:08","slug":"grass-carp-ctenopharyngodon-idella-smyd3-negatively-regulates-antiviral-innate-immunity-by-methylating-irf3-and-irf7-during-gcrv-infection","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2025\/11\/16\/grass-carp-ctenopharyngodon-idella-smyd3-negatively-regulates-antiviral-innate-immunity-by-methylating-irf3-and-irf7-during-gcrv-infection\/","title":{"rendered":"Grass carp (Ctenopharyngodon idella) SMYD3 negatively regulates antiviral innate immunity by methylating IRF3 and IRF7 during GCRV infection"},"content":{"rendered":"<div>\n<p><b>J Immunol<\/b>. 2025 Nov 15:vkaf311. doi: 10.1093\/jimmun\/vkaf311. Online ahead of print.<\/p>\n<p><b>ABSTRACT<\/b><\/p>\n<p>Interferon regulatory factors 3 and 7 (IRF3 and IRF7, respectively), which serve as key transcription factors in interferon (IFN) activation, are tightly regulated by a variety of mechanisms, including multiple posttranslational modifications, to fulfill their normal physiological functions. Nevertheless, the methylation-mediated regulation of IRF3 and IRF7 in grass carp (Ctenopharyngodon idella) remains poorly understood. In this study, we found that SMYD3, a lysine methyltransferase, is conserved across species and is induced by grass carp reovirus (GCRV) infection in grass carp. Furthermore, overexpression of grass carp SMYD3 exerted a negative regulatory effect on antiviral innate immunity. Conversely, knocking down of SMYD3 in cells enhanced the GCRV-induced antiviral gene expression. Mechanistically, SMYD3 interacts with the transcription factors IRF3 and IRF7, as demonstrated by co-immunoprecipitation and immunofluorescence confocal microscopy assays. Moreover, SMYD3 was found to orchestrate the di- or tri-methylation of the fifth lysine of IRF3 and the 11th lysine of IRF7, as identified by mass spectrometry. Furthermore, treatment with the SMYD3-specific inhibitor BCI121 significantly enhanced resistance to GCRV infection in cells and grass carp. Our results reveal a novel function of the lysine methyltransferase SMYD3 in anti-GCRV immunity and identify SMYD3 as a potential target for breeding new grass carp strains with anti-GCRV ability. In addition, our findings suggest that BCI121, a SMYD3-specific small molecule inhibitor, can be developed as an effective anti-GCRV drug for the treatment of grass carp hemorrhagic disease caused by GCRV.<\/p>\n<p>PMID:<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/41240378\/?utm_source=SimplePie&amp;utm_medium=rss&amp;utm_content=2985117R&amp;ff=20251115184607&amp;v=2.18.0.post22+67771e2\">41240378<\/a> | DOI:<a href=\"https:\/\/doi.org\/10.1093\/jimmun\/vkaf311\">10.1093\/jimmun\/vkaf311<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>J Immunol. 2025 Nov 15:vkaf311. doi: 10.1093\/jimmun\/vkaf311. Online ahead of print. ABSTRACT Interferon regulatory factors 3 and 7 (IRF3 and IRF7, respectively), which serve as key transcription factors in interferon (IFN) activation, are tightly regulated by a variety of mechanisms, including multiple posttranslational modifications, to fulfill their normal physiological functions. Nevertheless, the methylation-mediated regulation of &#8230; <a title=\"Grass carp (Ctenopharyngodon idella) SMYD3 negatively regulates antiviral innate immunity by methylating IRF3 and IRF7 during GCRV infection\" class=\"read-more\" href=\"https:\/\/inmuno.es\/index.php\/2025\/11\/16\/grass-carp-ctenopharyngodon-idella-smyd3-negatively-regulates-antiviral-innate-immunity-by-methylating-irf3-and-irf7-during-gcrv-infection\/\" aria-label=\"Read more about Grass carp (Ctenopharyngodon idella) SMYD3 negatively regulates antiviral innate immunity by methylating IRF3 and IRF7 during GCRV infection\">Read more<\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[42,71],"tags":[],"class_list":["post-48857","post","type-post","status-publish","format-standard","hentry","category-publicaciones","category-the-journal-of-immunology"],"_links":{"self":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/48857","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/comments?post=48857"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/48857\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=48857"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=48857"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=48857"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}