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<p>The vitamin A metabolite all-<i>trans</i> retinoic acid (ATRA) has immunoregulatory features, but its systemic role during viral infection is unclear. Here we show that patients infected with severe fever with thrombocytopenia syndrome virus (SFTSV), an emerging tick-borne infection, have depleted serum vitamin A and ATRA levels. This correlated with exacerbated systemic inflammatory response syndrome severity and mortality risk. In an SFTSV mouse model, intraperitoneal administration of ATRA suppresses virus-induced hyperinflammation via peroxisome proliferator-activated receptor-γ (PPARγ), which downregulates the transcriptional activity of activator protein-1 (AP-1 in macrophages. Mechanistically, ATRA binds retinoid X receptor-α (RXRα) and facilitates the formation of RXRα–PPARγ heterodimers. This complex sequesters the transcription factor JUN and suppresses the expression of AP-1 promoter-dependent genes, such as IL-6, thus attenuating inflammatory signalling pathways. Our study suggests a retinoid-mediated immunometabolic checkpoint during SFTSV infection and proposes retinoid signalling as a therapeutic target for cytokine storm management.</p>

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All-trans retinoic acid suppresses systemic inflammation induced by severe fever with thrombocytopenia syndrome virus in mice

  • 期刊论文

  • 发表日期：

    2026年7月20日

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  • Xin Yu,
  • Jianan Wu,
  • Xiaohong Yin,
  • Mengjia Yue,
  • Yunfa Zhang,
  • Jinxin Meng,
  • Jinyan Xie,
  • Jialei Li,
  • Xiaoai Zhang,
  • Ning Cui,
  • Zhen Wang,
  • Zhi-You Wang,
  • Wen-Wen Zhang,
  • Xinyu Ni,
  • Shuxian Chen,
  • Hao Li,
  • Wei Liu,
  • Shu Jeffrey Zhu

摘要

The vitamin A metabolite all-trans retinoic acid (ATRA) has immunoregulatory features, but its systemic role during viral infection is unclear. Here we show that patients infected with severe fever with thrombocytopenia syndrome virus (SFTSV), an emerging tick-borne infection, have depleted serum vitamin A and ATRA levels. This correlated with exacerbated systemic inflammatory response syndrome severity and mortality risk. In an SFTSV mouse model, intraperitoneal administration of ATRA suppresses virus-induced hyperinflammation via peroxisome proliferator-activated receptor-γ (PPARγ), which downregulates the transcriptional activity of activator protein-1 (AP-1 in macrophages. Mechanistically, ATRA binds retinoid X receptor-α (RXRα) and facilitates the formation of RXRα–PPARγ heterodimers. This complex sequesters the transcription factor JUN and suppresses the expression of AP-1 promoter-dependent genes, such as IL-6, thus attenuating inflammatory signalling pathways. Our study suggests a retinoid-mediated immunometabolic checkpoint during SFTSV infection and proposes retinoid signalling as a therapeutic target for cytokine storm management.