Experimental Study on the Anti-HP-PRRSV Effect of Manganese Ion-Mediated NF-κB Signaling Pathway

Experimental Study on the Anti-HP-PRRSV Effect of Manganese Ion-Mediated NF-κB Signaling Pathway | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Experimental Study on the Anti-HP-PRRSV Effect of Manganese Ion-Mediated NF-κB Signaling Pathway Jianming Yang, Mengyu Zou, Yuyan Cen, Huan Mao, Cheng Liu, Shunyu Xiang, and 10 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9027364/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract The precise antiviral mechanism of manganese ions (Mn²⁺) remains incompletely understood. In this study, we elucidated how Mn²⁺ counteracts highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) infection and defined its link to the NF-κB signaling pathway. First, we determined that 10 µM MnCl₂ was the maximum non-toxic dose on Marc-145 cells. Pretreatment with MnCl₂ at this dose before HP-PRRSV infection significantly inhibited viral replication, as evidenced by reduced viral titers and viral N protein expression, while also alleviating cytopathic effects and downregulating the secretion of pro-inflammatory cytokines IL-6 and IL-8. Mechanistically, HP-PRRSV infection suppressed the activation of the NF-κB pathway, indicated by decreased phosphorylation levels of p65 and IκBα. MnCl₂ pretreatment effectively reversed this suppression. Furthermore, it concurrently upregulated the expression of antiviral interferons, IFN-α and IFN-β. Crucially, functional validation using the specific NF-κB agonist Diproqualone (Dip-1) mimicked the antiviral effect of Mn²⁺, whereas inhibition of the pathway with BAY 11-7082 exacerbated infection and suppressed interferon production. Collectively, these findings demonstrate that manganese antagonizes HP-PRRSV infection by activating the NF-κB signaling pathway, which in turn induces a potent interferon response. Full Text Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9027364","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":608614435,"identity":"b0d24f04-763e-40c2-9cb3-73a527e6d18b","order_by":0,"name":"Jianming Yang","email":"","orcid":"","institution":"People's Hospital of Qianxinan Prefecture","correspondingAuthor":false,"prefix":"","firstName":"Jianming","middleName":"","lastName":"Yang","suffix":""},{"id":608614437,"identity":"a95479af-cd79-4d0d-a165-eea09173fed8","order_by":1,"name":"Mengyu Zou","email":"","orcid":"","institution":"Zunyi Medical University School of Public 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In this study, we elucidated how Mn\u0026sup2;⁺ counteracts highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) infection and defined its link to the NF-κB signaling pathway. First, we determined that 10 \u0026micro;M MnCl₂ was the maximum non-toxic dose on Marc-145 cells. Pretreatment with MnCl₂ at this dose before HP-PRRSV infection significantly inhibited viral replication, as evidenced by reduced viral titers and viral N protein expression, while also alleviating cytopathic effects and downregulating the secretion of pro-inflammatory cytokines IL-6 and IL-8. Mechanistically, HP-PRRSV infection suppressed the activation of the NF-κB pathway, indicated by decreased phosphorylation levels of p65 and IκBα. MnCl₂ pretreatment effectively reversed this suppression. Furthermore, it concurrently upregulated the expression of antiviral interferons, IFN-α and IFN-β. Crucially, functional validation using the specific NF-κB agonist Diproqualone (Dip-1) mimicked the antiviral effect of Mn\u0026sup2;⁺, whereas inhibition of the pathway with BAY 11-7082 exacerbated infection and suppressed interferon production. Collectively, these findings demonstrate that manganese antagonizes HP-PRRSV infection by activating the NF-κB signaling pathway, which in turn induces a potent interferon response.\u003c/p\u003e","manuscriptTitle":"Experimental Study on the Anti-HP-PRRSV Effect of Manganese Ion-Mediated NF-κB Signaling Pathway","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-03-20 20:43:54","doi":"10.21203/rs.3.rs-9027364/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"5bfe6df3-b7c9-4ead-b869-f345a10d9b32","owner":[],"postedDate":"March 20th, 2026","published":true,"recentEditorialEvents":[{"type":"decision","content":"Rejected","date":"2026-05-08T13:36:52+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-04T05:28:08+00:00","index":31,"fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-05-08T13:44:48+00:00","versionOfRecord":[],"versionCreatedAt":"2026-03-20 20:43:54","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9027364","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9027364","identity":"rs-9027364","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}