Characterization of a reassortant H3N2 swine influenza virus with 2009 pandemic internal genes and enhanced potential for zoonotic risk.
Jun Jiao1,2,3,4
Jin Ding1,2,3,5
Ziyan Sun1,2,3,6
Chenglin Chi1,2,3,7
Sizhuang Liu1,2,3,8
Sen Jiang1,2,3,9
Nanhua Chen1,2,3,10
Wanglong Zheng1,2,3,11
Xiaoyan Ding12
Jianzhong Zhu1,2,3,13
Affiliations13 institutions
College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China
Comparative Medicine Research Institute, Yangzhou University, Yangzhou 225009, China
Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou 225009, China
Jiangsu Interdisciplinary Center for Zoonoses and Biosafety, Jiangsu Key Laboratory of Zoonosis, Yangzhou University, Yangzhou 225009, PR China. Electronic address: [email protected].
Jiangsu Interdisciplinary Center for Zoonoses and Biosafety, Jiangsu Key Laboratory of Zoonosis, Yangzhou University, Yangzhou 225009, PR China. Electronic address: [email protected].
Jiangsu Interdisciplinary Center for Zoonoses and Biosafety, Jiangsu Key Laboratory of Zoonosis, Yangzhou University, Yangzhou 225009, PR China. Electronic address: [email protected].
Jiangsu Interdisciplinary Center for Zoonoses and Biosafety, Jiangsu Key Laboratory of Zoonosis, Yangzhou University, Yangzhou 225009, PR China. Electronic address: [email protected].
Jiangsu Interdisciplinary Center for Zoonoses and Biosafety, Jiangsu Key Laboratory of Zoonosis, Yangzhou University, Yangzhou 225009, PR China. Electronic address: [email protected].
Jiangsu Interdisciplinary Center for Zoonoses and Biosafety, Jiangsu Key Laboratory of Zoonosis, Yangzhou University, Yangzhou 225009, PR China. Electronic address: [email protected].
Jiangsu Interdisciplinary Center for Zoonoses and Biosafety, Jiangsu Key Laboratory of Zoonosis, Yangzhou University, Yangzhou 225009, PR China. Electronic address: [email protected].
Jiangsu Interdisciplinary Center for Zoonoses and Biosafety, Jiangsu Key Laboratory of Zoonosis, Yangzhou University, Yangzhou 225009, PR China. Electronic address: [email protected].
Pigs serve as key "mixing vessels" for influenza A viruses, playing a critical role in cross-species transmission, while the H3N2 subtype represents an important lineage within the swine influenza virus (SIV) family. In this study, a novel reassortant H3N2 SIV strain, designated A/Swine/Jiangsu/YZ07/2024, was isolated from pigs exhibiting clinical symptoms in Northern Jiangsu, China during epidemiological survey. Genetic analysis revealed that the virus is a complex reassortant, with the internal genes (M, NP, PB1, PB2, PA) originated from the 2009 pandemic H1N1 lineage, the NS gene exhibiting a North American triple reassortant origin (human-avian-swine origin), and the HA and NA genes belonging to the human-like lineage. Although neither the rescued virus nor its parental strain could replicate effectively in chicken embryos and chicken cells, both demonstrated efficient replication in mammalian cells, reflected by the much higher polymerase activity in mammalian versus chicken cells. The key residues of HA protein (190D, 225D and 228S) collectively enhanced the binding preference for human-type α-2,6-linked sialic acid receptors, which was confirmed by receptor binding assays. Furthermore, mouse infection experiments using the rescued H3N2 demonstrated efficient viral replication in nasal turbinates and lung tissues, accompanied by significant pulmonary pathological damage. These findings indicate that the YZ07 strain, through the vast reassortment and accumulation of adaptive mutations, has acquired potential zoonotic risk, underscoring the importance of surveillance of swine influenza viruses.
The H3N2 swine influenza virus replicated poorly in chicken embryos and chicken cells but efficiently in mammalian cells, showing host-specific replication capacity.
Neither the rescued virus nor its parental strain could replicate effectively in chicken embryos and chicken cells, both demonstrated efficient replication in mammalian cells, reflected by the higher polymerase activity in mammalian versus chicken cells.
Method
replication assay; polymerase activity assay
Experimental system
in vitro cell culture
Host Range ExperimentExtraction confidence 0.90
Key finding
The H3N2 swine influenza virus showed efficient replication in mammalian cells, consistent with enhanced mammalian tropism.
Neither the rescued virus nor its parental strain could replicate effectively in chicken embryos and chicken cells, both demonstrated efficient replication in mammalian cells, reflected by the higher polymerase activity in mammalian versus chicken cells.
Method
replication assay; polymerase activity assay
Experimental system
in vitro cell culture
Host Range ExperimentExtraction confidence 0.90
Key finding
In vivo mouse infection showed replication of the H3N2 virus in nasal turbinates and lungs, causing pulmonary lesions.
Mouse infection experiments using the rescued H3N2 demonstrated efficient viral replication in nasal turbinates and lung tissues, accompanied by significant pulmonary pathological damage.
Residues 190D, 225D, and 228S in the HA protein of the H3N2 swine influenza virus increase binding to human-type α-2,6-linked sialic acid receptors, indicating adaptation toward human hosts.
The key residues of HA protein (190D, 225D and 228S) collectively enhanced the binding preference for human-type α-2,6-linked sialic acid receptors, which was confirmed by receptor binding assays.
Genes or proteins
HA
Receptors
α-2,6-linked sialic acid receptors
Mutations
190D; 225D; 228S
Mechanism types
receptor_binding
Molecular AdaptationExtraction confidence 0.90
Key finding
The reassortant H3N2 swine influenza virus displays higher polymerase activity and enhanced replication efficiency in mammalian cells compared to avian cells.
Both demonstrated efficient replication in mammalian cells, reflected by the much higher polymerase activity in mammalian versus chicken cells.
Mechanism types
polymerase_activity; replication_efficiency
Genomic Evolution1 records
Genomic EvolutionExtraction confidence 0.80
Key finding
The H3N2 swine influenza virus A/Swine/Jiangsu/YZ07/2024 shows genomic evolution through reassortment with internal genes from 2009 pandemic H1N1 and surface genes of human-like origin, indicating cross-lineage mixing and potential host adaptation.
Genetic analysis revealed that the virus is a complex reassortant, with the internal genes (M, NP, PB1, PB2, PA) originated from the 2009 pandemic H1N1 lineage, the NS gene exhibiting a North American triple reassortant origin (human-avian-swine origin), and the HA and NA genes belonging to the human-like lineage.
Genes or proteins
M; NP; PB1; PB2; PA; NS; HA; NA
Analysis methods
genetic analysis; phylogenetic analysis
Receptor Usage1 records
Receptor UsageExtraction confidence 0.95
Key finding
A/Swine/Jiangsu/YZ07/2024 H3N2 swine influenza virus shows enhanced human-type α-2,6-linked sialic acid receptor binding mediated by HA residues 190D, 225D, and 228S.
The key residues of HA protein (190D, 225D and 228S) collectively enhanced the binding preference for human-type α-2,6-linked sialic acid receptors, which was confirmed by receptor binding assays.
Method
receptor binding assay
Receptors
α-2,6-linked sialic acid receptor
Recombination Or Reassortment1 records
Recombination Or ReassortmentExtraction confidence 1.00
Key finding
The A/Swine/Jiangsu/YZ07/2024 H3N2 swine influenza virus is a complex reassortant carrying internal genes from pandemic H1N1 and possessing additional human and triple reassortant gene origins, contributing to its enhanced zoonotic potential.
In this study, a novel reassortant H3N2 SIV strain, designated A/Swine/Jiangsu/YZ07/2024, was isolated from pigs ... Genetic analysis revealed that the virus is a complex reassortant, with the internal genes (M, NP, PB1, PB2, PA) originated from the 2009 pandemic H1N1 lineage, the NS gene exhibiting a North American triple reassortant origin (human-avian-swine origin), and the HA and NA genes belonging to the human-like lineage.
Event type
reassortment
Genes or segments
M; NP; PB1; PB2; PA; NS; HA; NA
Zoonotic Surveillance1 records
Zoonotic SurveillanceExtraction confidence 0.90
Key finding
A reassortant H3N2 swine influenza virus was identified from clinically affected pigs during epidemiological surveillance in Northern Jiangsu, China.
In this study, a novel reassortant H3N2 SIV strain, designated A/Swine/Jiangsu/YZ07/2024, was isolated from pigs exhibiting clinical symptoms in Northern Jiangsu, China during epidemiological survey.
