{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T00:05:50Z","timestamp":1793145950143,"version":"4.5.0"},"reference-count":54,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T00:00:00Z","timestamp":1782172800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T00:00:00Z","timestamp":1782172800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100003819","name":"Natural Science Foundation of Hubei Province","doi-asserted-by":"crossref","award":["2024AFA024"],"award-info":[{"award-number":["2024AFA024"]}],"id":[{"id":"10.13039\/501100003819","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2026,6,23]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>The Nipah virus (NiV) matrix (M) protein, essential for viral assembly, has been increasingly recognized for its potential immunomodulatory functions. However, its role in modulating the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-\u03baB) signaling pathway\u2014a central regulator of inflammation and innate immunity\u2014remains poorly defined. Here, we demonstrate that NiV-M significantly promotes activation of the classical NF-\u03baB pathway. Our data showed that NiV-M interacts with multiple cellular signaling molecules of the NF-\u03baB pathway, including tripartite motif containing 25 (TRIM25), inhibitor of nuclear factor kappa-B kinase subunit alpha (IKK\u03b1), nuclear factor of kappa light polypeptide gene enhancer in B-cell inhibitor alpha (I\u03baB\u03b1), and the p65 subunit of NF-\u03baB. Further analyses revealed that NiV-M enhanced the E3 ubiquitin ligase activity of TRIM25, facilitating its interaction with both retinoic acid-inducible gene I (RIG-I) and TNF receptor-associated factor 2 (TRAF2), thereby promoting K63-linked ubiquitination of RIG-I and TRAF2. Moreover, NiV-M strengthened the interaction between IKK\u03b1 and IKK\u03b2, leading to enhanced IKK complex activity and accelerated degradation of I\u03baB\u03b1. In addition, NiV-M promoted phosphorylation and nuclear translocation of p65, thereby amplifying NF-\u03baB-driven gene expression. In summary, our results demonstrate a multifaceted strategy by which NiV-M regulates the NF-\u03baB pathway, a mechanism that may contribute to NiV pathogenesis via inflammatory dysregulation. These findings suggest potential therapeutic approaches for alleviating symptoms associated with immunopathology of NiV by targeting virus\u2013host interactions.<\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>This study reveals a previously unknown role of the Nipah virus matrix (M) protein in driving excessive inflammation, a key factor in the virus\u2019s high mortality. We discovered that the M protein acts as a master switch, hijacking a central human immune pathway (NF-\u03baB) at multiple points to trigger a \u201ccytokine storm.\u201d This explains how the virus causes severe tissue damage and organ failure in infected individuals. By identifying the specific human proteins targeted by the M protein, our work establishes that this viral component functions not only in viral assembly but also in the dysregulation of host inflammatory responses, thereby providing a new perspective on its potential contribution to severe NiV-associated disease. These findings open new avenues for treating NiV infections by developing drugs that target these interactions, potentially controlling the devastating inflammation rather than just the virus itself.<\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/jvi.00185-26","type":"journal-article","created":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T13:48:11Z","timestamp":1779371291000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":1,"title":["Nipah virus matrix protein promotes NF-\u03baB activation by targeting multiple signaling modulators"],"prefix":"10.1128","volume":"100","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-5472-7539","authenticated-orcid":false,"given":"Chang","family":"Ye","sequence":"first","affiliation":[{"name":"State Key Laboratory of Virology and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences","place":["Wuhan, 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