Key Laboratory of Avian Bioproducts Development, Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China
Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis, Yangzhou University, Yangzhou 225009, China
Jiangsu Key Laboratory of Zoonosis, Yangzhou 225009, China.
College of Medicine, Yangzhou University, Yangzhou 225009, China.
Clade 2.3.4.4b H5Nx highly pathogenic avian influenza viruses (HPAIVs) have caused extensive outbreaks in poultry worldwide. H5 HPAIVs have caused sporadic but severe human infections in China, representing a persistent zoonotic threat. Here, we identified a duck-origin H5N6 HPAIV (A/Duck/Jiangsu/628/2022) through routine surveillance and assessed its biological characteristics and mammalian pathogenesis. Phylogenetic analysis revealed > 98% nucleotide identity between strain 628 and the concurrent human H5N6 strain A/Yangzhou/125/2022. Molecular characterization identified multiple mammalian adaptation markers: hemagglutinin substitutions (S137A, T160A, T192I) associated with enhanced human receptor binding; neuraminidase mutations (I117T, D198N) linked to reduced neuraminidase inhibitor susceptibility; and polymerase complex changes (PB1-D622G, PA-K142Q) conferring increased mammalian cell replication. In vitro studies demonstrated that 628 virus replicated more efficiently in mammalian than in avian cells and exhibited dual receptor-binding specificity. Mouse pathogenicity assays revealed moderate virulence with progressive lung pathology. Critically, transmission experiments confirmed both direct contact and airborne transmission capabilities of 628 in guinea pigs. These findings demonstrate that circulating H5N6 viruses have acquired partial mammalian adaptation while retaining avian fitness, significantly elevating pandemic potential. Enhanced surveillance of wild bird populations, poultry farms, and live poultry markets is urgently needed to develop effective prevention and control strategies.
Duck-OriginH5N6PathogenicityTransmissibility
Structured evidence records
Evidence records
8 total
Host Range Experiment3 records
Host Range ExperimentExtraction confidence 0.95
Key finding
Duck-origin H5N6 virus showed increased replication in mammalian cells and was transmissible by contact and airborne routes in guinea pigs, indicating cross-species host adaptation.
In vitro studies demonstrated that 628 virus replicated more efficiently in mammalian than in avian cells and exhibited dual receptor-binding specificity. Mouse pathogenicity assays revealed moderate virulence with progressive lung pathology. Critically, transmission experiments confirmed both direct contact and airborne transmission capabilities of 628 in guinea pigs.
Method
replication assay
Experimental system
in vitro cell culture
Host Range ExperimentExtraction confidence 0.95
Key finding
Duck-origin H5N6 virus caused moderate disease and lung pathology in experimentally infected mice.
Transmission experiments confirmed both direct contact and airborne transmission capabilities of 628 in guinea pigs.
Method
transmission experiment
Experimental system
in vivo animal experiment
Cross Species Transmission1 records
Cross Species TransmissionExtraction confidence 0.92
Key finding
A duck-origin clade 2.3.4.4b H5N6 avian influenza virus was able to transmit by direct contact and airborne routes among guinea pigs, showing animal-to-animal cross-species transmissibility.
Transmission experiments confirmed both direct contact and airborne transmission capabilities of 628 in guinea pigs.
Method
transmission experiment; pathogenicity assay
Study design
animal experiment
Transmission direction
animal-to-animal
Geographic raw
Jiangsu
Country inferred
China
Genomic Evolution1 records
Genomic EvolutionExtraction confidence 0.88
Key finding
Phylogenetic and molecular analysis showed that the duck-origin H5N6 virus was closely related to a human H5N6 strain and contained multiple mutations associated with mammalian adaptation.
Phylogenetic analysis revealed > 98% nucleotide identity between strain 628 and the concurrent human H5N6 strain A/Yangzhou/125/2022. Molecular characterization identified multiple mammalian adaptation markers: hemagglutinin substitutions (S137A, T160A, T192I)... neuraminidase mutations (I117T, D198N)... and polymerase complex changes (PB1-D622G, PA-K142Q).
Genes or proteins
hemagglutinin; neuraminidase; polymerase complex; PB1; PA
Analysis methods
phylogenetic analysis; molecular characterization
Molecular Adaptation1 records
Molecular AdaptationExtraction confidence 0.98
Key finding
The duck-origin H5N6 virus exhibited hemagglutinin, neuraminidase, and polymerase mutations corresponding to partial adaptation to mammalian hosts through enhanced receptor binding, drug resistance, and improved replication efficiency.
The duck-origin H5N6 virus contains HA mutations that enhance human receptor binding and demonstrate dual receptor-binding specificity consistent with partial mammalian receptor adaptation.
Molecular characterization identified multiple mammalian adaptation markers: hemagglutinin substitutions (S137A, T160A, T192I) associated with enhanced human receptor binding, and in vitro studies showed dual receptor-binding specificity.
Method
molecular characterization; in vitro replication assay
Receptors
human receptor
Zoonotic Surveillance1 records
Zoonotic SurveillanceExtraction confidence 0.90
Key finding
A duck-origin H5N6 avian influenza virus was detected in Jiangsu, China via routine surveillance among ducks, reflecting active monitoring for zoonotic influenza circulation.
Here, we identified a duck-origin H5N6 HPAIV (A/Duck/Jiangsu/628/2022) through routine surveillance and assessed its biological characteristics and mammalian pathogenesis.
