2. Academic Validation
  3. STING-NF-κB signaling builds an influenza spillover barrier

STING-NF-κB signaling builds an influenza spillover barrier

  • Science. 2026 Feb 26;391(6788):eads4405. doi: 10.1126/science.ads4405.
Runxin Ye # 1,  Songdi Wang # 1,  Ying Hu # 1,  Yiran Pan 1,  Wenwen Zheng 1,  Fengyan Xia 1,  Yanpu Wang 1,  Haoran Guo 2 3,  Shu Zheng 1,  Wei Wei 2 3,  Xiao-Fang Yu 1 4 5
Affiliations

Affiliations

  • 1 Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
  • 2 Cancer Center Key Laboratory of Organ Regeneration and Transplantation of Ministry of Education, Institute of Translational Medicine, First Hospital, Jilin University, Changchun, China.
  • 3 Institute of Virology and AIDS Research, First Hospital, Jilin University, Changchun, China.
  • 4 Zhejiang Provincial Clinical Research Center for CANCER, Hangzhou, Zhejiang, China.
  • 5 Cancer Center of Zhejiang University, Hangzhou, Zhejiang, China.
  • # Contributed equally.
PMID: 41747053 DOI: 10.1126/science.ads4405
Abstract

Influenza pandemics are often traced back to the spillover of avian influenza A viruses (IAVs) to humans. However, barriers against IAV transmission remain elusive. We demonstrated human stimulator of interferon genes (STING) as a transmission barrier against IAVs. STING activated nuclear factor κB (NF-κB) and downstream NF-κB-stimulated genes (NSGs) through a specific domain. Among these NSGs, growth arrest and DNA damage-inducible protein 34 (GADD34) was crucial for IAV restriction. Some IAVs have evolved to evade activating human STING by mutating residue 115 in their Matrix Protein 1 (M1), which is essential for efficient viral replication in human respiratory cells. This barrier against the zoonotic threat of IAVs provides a tool for future investigations into the biological functions of the cyclic guanosine monophosphate-adenosine monosphosphate (cGMP-AMP) synthase (cGAS)-STING-NF-κB signaling pathway.

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