{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:08:27Z","timestamp":1785434907359,"version":"3.56.0"},"reference-count":43,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T00:00:00Z","timestamp":1784592000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T00:00:00Z","timestamp":1784592000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022YFD1800300"],"award-info":[{"award-number":["2022YFD1800300"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2023YFF1000901"],"award-info":[{"award-number":["2023YFF1000901"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2026,7,21]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Porcine reproductive and respiratory syndrome (PRRS) caused by PRRS virus (PRRSV) is a highly contagious disease that severely threatens the global pig industry. A significant symptom of PRRS is severe pneumonia. At present, studies have shown that IL-1\u03b2 is upregulated by PRRSV infection\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      , while the underlying mechanism remains unknown. Here, we explored how PRRSV regulated IL-1\u03b2 production. We found that HP-PRRSV nsp1 upregulated the expression of IL-1\u03b2. Overexpression of nsp1 induced IL-1\u03b2 production in a dose-dependent manner. Subsequently, we demonstrated that nsp1 enhanced IL-1\u03b2 expression by activating JNK\/p38 signaling pathways, as the addition of p38 and JNK inhibitors reduced IL-1\u03b2 production induced by nsp1. Moreover, deleting the AP-1 binding motif in porcine IL-1\u03b2 promoter impaired IL-1\u03b2 expression induced by nsp1, suggesting that AP-1 is essential for IL-1\u03b2 production. In addition, we showed that TRAF6 was required for nsp1 to activate the TAK1\/JNK\/p38\/AP-1 signaling pathway by interacting with each other. Truncation and deletion mutation analysis indicated that R308 and R375 amino acids were important for nsp1 to interact with TRAF6 and induce IL-1\u03b2 production. Finally, we constructed the recombinant viruses mutated at R308 and R375 and found that the mutated virus PRRSV-R308\/375A exhibited a significantly reduced replication rate and impaired the ability to induce IL-1\u03b2 compared to the wild-type strain. These findings provide new insights into the molecular mechanisms of IL-1\u03b2 production induced by PRRSV and help us further understand the pathogenesis of PRRSV infection.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        Highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) has been prevalent in China since 2006, causing severe pneumonia in pigs. IL-1\u03b2 is a proinflammatory cytokine secreted by various cells. In this study, we demonstrated that PRRSV protein nsp1 interacted with TRAF6 to activate the TAK1\/JNK\/p38\/AP-1 signaling pathway, consequently inducing the expression of IL-1\u03b2. Additionally, our findings revealed that R308 and R375 in nsp1 were critical amino acid residues for nsp1 to interact with TRAF6 and induce IL-1\u03b2 production. Notably, the recombinant virus PRRSV-R308\/375A exhibited a significantly reduced replication rate and impaired ability to induce proinflammatory cytokines\n                        <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                        compared to the wild-type strain HP-PRRSV. This study helps us further understand HP-PRRSV pathogenesis and provides a new idea for the development of PRRSV vaccines.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/jvi.00428-26","type":"journal-article","created":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T14:16:36Z","timestamp":1781273796000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Highly pathogenic porcine reproductive and respiratory syndrome virus nonstructural protein 1 interacts with TRAF6 to activate the TAK1\/p38\/JNK\/AP-1 signaling and induce IL-1\u03b2"],"prefix":"10.1128","volume":"100","author":[{"given":"Jiaying","family":"Zhu","sequence":"first","affiliation":[{"name":"Frontiers Science Center for Molecular Design Breeding","place":["Beijing, China"]},{"name":"State Key Laboratory of Animal Biotech Breeding","place":["Beijing, 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