A research team of SAHZU has published a study in the journal Science identifying a critical immune pathway that helps block influenza viruses from spreading from animals to humans.

The paper, titled "STING–NF-κB signaling builds an influenza spillover barrier," reveals a mechanism in the human innate immune system that restricts avian influenza A viruses (IAV). The research was conducted at the Cancer Institute, where Prof. YU serves as director.

Key Discovery

The team found that the immune signaling protein STING is activated during influenza virus infection. Once activated, STING triggers the NF-κB pathway to suppress viral replication, acting as a natural barrier against the virus.

A specific amino acid residue on the STING protein—glycine at position 90 (Gly90)—was identified as a crucial "switch" for activating this antiviral signal. When this switch is turned on, it limits flu virus replication.

Furthermore, the research systematically characterized a new class of antiviral molecules called NF-κB-stimulating genes (NSGs). Among them, the molecule GADD34 was shown to play a key role by targeting the virus's replication machinery.

Implications for Pandemic Monitoring

The study also sheds light on why some flu viruses transmit easily among humans while others remain largely in animals. The team demonstrated that the M1 protein from human-adapted influenza viruses can effectively counteract the human STING–NF-κB–GADD34 antiviral pathway, whereas the M1 protein from avian viruses is much less effective.

A specific mutation in the M1 protein—at amino acid position 115—was identified as a key factor enhancing the virus's ability to overcome this human immune defense.

Prof. YU noted that this discovery could provide a molecular marker for monitoring the pandemic potential of avian influenza viruses. "If we see this mutation appearing in viruses circulating in birds, it could serve as an early warning sign of increased risk for human infection," he suggested.

About the team

Prof. YU, who joined SAHZU full-time in 2016 after a distinguished career at Johns Hopkins University, has studied virology and host immunity for over four decades. His work bridges basic research in immunology with potential applications in infectious disease control and cancer immunology.

This publication adds to a series of recent high-impact research from SAHZU, which has seen papers published in  Cell, The Lancet, NEJM, JAMA, and The BMJ in recent years.