{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T14:18:32Z","timestamp":1785421112930,"version":"3.56.0"},"reference-count":52,"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"}],"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>While adaptive humoral immunity and type\u202fI interferon (IFN-I) responses are known to cross-regulate each other during viral infection, the mechanisms by which antibodies (Abs) or immune complexes (ICs) modulate IFN-I signaling in immune cells remain unclear. Here, using plate-coated human IgG (cIgG) as an antigen-independent IC mimic, we show that Fc\u03b3RIIa cross-linking in human blood monocytes induces the expression of TRIM54, an E3 ubiquitin ligase previously thought to be constitutively expressed only in muscle tissue. Mechanistically, TRIM54 binds to and promotes the ubiquitination of the transcriptional activator STAT2, thereby dampening the expression of many IFN-stimulated genes. This inhibitory role is functionally corroborated by a positive correlation between elevated TRIM54 levels and enhanced cellular permissiveness to infection by vesicular stomatitis virus, Dengue virus, and\/or Sendai virus, in cIgG-primed human monocytes, and monocytic cell lines with genetically modulated TRIM54 expression. Clinically, elevated TRIM54 expression is detected in circulating monocytes from pediatric patients with Epstein-Barr virus-induced infectious mononucleosis. Together, our findings define a previously unrecognized Fc\u03b3RIIa\u2013TRIM54\u2013STAT2 signaling axis through which virus-specific Abs\u2014particularly at sub-neutralizing concentrations\u2014can attenuate the IFN-I response in innate immune cells. This axis may also provide a mechanistic explanation for Ab-dependent enhancement of viral infection.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>The long-standing question of how antigen-antibody immunocomplexes regulate type I interferon (IFN) signaling in immune cells remains unanswered. Our study uncovers a novel pathway for negative regulation of IFN-I signaling via the Fc\u03b3RIIa-TRIM54-STAT2 axis in human monocytes. The novel concept will provide new insights into cross-regulation between humoral immunity and IFN response, and may provide important clues for the molecular mechanisms behind antibody-dependent enhancement of virus infection.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/jvi.02106-25","type":"journal-article","created":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T11:00:45Z","timestamp":1780052445000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["A novel Fc\u03b3RIIa-TRIM54-STAT2 axis negatively regulates type I interferon signaling and promotes viral susceptibility in human monocytes"],"prefix":"10.1128","volume":"100","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-7951-8577","authenticated-orcid":false,"given":"Xiao-Qiu","family":"Dai","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05kvm7n82","id-type":"ROR","asserted-by":"publisher"}],"name":"School of 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