λ-Carrageenan regulates antiviral responses by targeting classical NF-κB and IRF3-mediated signaling pathways

  • Int J Biol Macromol. 2025 Dec 17;338(Pt 2):149760. doi: 10.1016/j.ijbiomac.2025.149760.
Xueke Sun  1 Wanzi Yao  2 Jiaqing Hu  3 Yu Zhang  1 Ruijing Liu  1 Wenjing Hu  1 Yongtao Li  1 Bo Wan  4 Zhengjie Kong  5 Gaiping Zhang  6
Affiliations
  • 1. College of Veterinary Medicine, Henan Agricultural University, Zhengzhou, Henan, China; International Joint Research Center for National Animal Immunology, Zhengzhou, Henan, China.
  • 2. School of Advanced Agricultural Sciences, Peking University, Beijing, China.
  • 3. Shandong Provincial Key Laboratory for Livestock Germplasm Innovation & Utilization, College of Animal Science and Technology, Shandong Agricultural University, Taian, China.
  • 4. College of Veterinary Medicine, Henan Agricultural University, Zhengzhou, Henan, China; International Joint Research Center for National Animal Immunology, Zhengzhou, Henan, China. Electronic address: [email protected].
  • 5. School of Advanced Agricultural Sciences, Peking University, Beijing, China. Electronic address: [email protected].
  • 6. College of Veterinary Medicine, Henan Agricultural University, Zhengzhou, Henan, China; International Joint Research Center for National Animal Immunology, Zhengzhou, Henan, China; School of Advanced Agricultural Sciences, Peking University, Beijing, China; Longhu Laboratory, Zhengzhou, China. Electronic address: [email protected].
Abstract

λ-Carrageenan (λ-CGN) has attracted attention for its biological activities, such as anticoagulant, antitumor, and pro-inflammatory effects. Here, we explored the function of λ-CGN in modulating innate immune responses. Our study showed that λ-CGN inhibited the Infection by various viruses. Mechanistically, λ-CGN mediated inflammatory responses by activating classical NF-κB signaling. Importantly, λ-CGN attenuated K48 ubiquitination of IRF3, thereby promoting IRF3 protein stability and activating IRF3-mediated type I IFN responses. Furthermore, orally administered λ-CGN attenuated the pathogenicity of PRV and VSV in mice. These results demonstrate a novel mechanism by which λ-CGN modulates immune responses and support λ-CGN as a potential Antiviral drug.

Keywords
Classical NF-κB; IRF3; Innate immunity; Λ-Carrageenan.
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