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However, the molecular mechanisms underlying its pathogenesis and immune evasion remain poorly defined. This study demonstrated that GETV infection suppressed the activation of interferon \u03b2 (IFN-\u03b2) or IFN-stimulated response element after poly(I:C) stimulation. By screening nine viral proteins (non-structural proteins 1\u20134 [nsP1\u20134] and C-E3-E2-6K-E1), we discovered that the nsP2 protein of GETV could effectively inhibit the production of IFN-\u03b2 and IFN-stimulated genes. Subsequently, we discovered that nsP2 disrupted the retinoic acid-inducible gene I-like receptor signaling pathway by causing widespread cellular shutoff and directly targeting inhibitor of kappa-B kinase \u03b5 (IKK\u03b5). Mechanistically, the inhibitory function of nsP2 is contingent upon the protein\u2019s structural integrity and the presence of proline 717 and nuclear localization signal-related residues. Additionally, we illustrated that nsP2 markedly inhibited TRAF2-induced K63-linked polyubiquitination and phosphorylation of IKK\u03b5, which is essential for activating IKK\u03b5. Altogether, the present study elucidated a new mechanism in which GETV modulates the host\u2019s antiviral immunity.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        <jats:italic toggle=\"yes\">Getah virus<\/jats:italic>\n                        (GETV), a multi-host alphavirus of the\n                        <jats:italic toggle=\"yes\">Togaviridae<\/jats:italic>\n                        family, imposes a significant economic burden on the swine industry by causing fever, diarrhea, reproductive disorders in sows, and elevated mortality in newborn piglets. Here, we reveal that GETV non-structural protein 2 antagonizes interferon \u03b2 (IFN-\u03b2) production through a dual mechanism: it induces broad cellular shutoff and directly interacts with inhibitor of kappa-B kinase \u03b5 (IKK\u03b5) to prevent its activation. This strategy effectively disrupts type I IFN responses by suppressing antiviral gene expression, such as IKK\u03b5, IFN-I, and IFN-stimulated genes, and impairing retinoic acid-inducible gene I-like receptor signaling activation. Our findings not only uncover a novel mechanism of GETV immune evasion but also establish the rationale for novel therapeutic targets, suggesting a new avenue for the treatment and intervention of GETV infection.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/spectrum.03419-25","type":"journal-article","created":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T13:00:18Z","timestamp":1780578018000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":2,"title":["<i>Getah virus<\/i>\n                    non-structural protein 2 inhibits type I interferon production by preventing K63-linked polyubiquitination of IKK\u03b5 and causing widespread cellular 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