Jiangsu Province - Credit Wikipedia
#19,216
It is not exactly a state secret that the Chinese CDC has become increasingly concerned over the evolution and spread of LPAI H9N2 in both poultry and people, particularly in the eastern provinces of China.
In addition to a human infection reported 10 days ago in Hong Kong, the CHP's latest weekly Avian Influenza report lists 15 known human infections on the mainland over the past 6 months.
While most (but not all) of these reported cases have been mild or moderate, its true incidence and burden in China is unknown. Most people with mild to moderate flu are never hospitalized, or tested, for novel flu.
Last October the Chinese CDC Weekly published a detailed report (see Epidemiological and Genetic Characterization of Three H9N2 Viruses Causing Human Infections — Changsha City, Hunan Province, China, April 2025) which found:
Three children infected with H9N2 AIV were identified in Changsha in April 2025, and no epidemiological links were found between these mild and sporadic cases. Genetic analysis showed that the H9N2 viruses had enhanced binding ability to upper respiratory tract receptors, particularly the α2,6-sialic acid receptors.
The report goes on describe some of the notable HA mutations suggesting enhanced mammalian adaptation:
Analysis of receptor-binding sites showed that the HA proteins had mutations at amino acid positions H191N, A198V, Q226L, and Q234L, which potentially enhanced the binding ability of the virus to the receptor (5-6).
While there is still no evidence of sustained or efficient human-to-human transmission of H9N2, the virus remains poorly controlled in poultry, and appears on a path towards greater mammalian adaptation.
LPAI H9N2 continues to evolve and diversify (see EM&I: A new clade of H9N2 avian influenza virus circulating in Laos), and our own CDC has assessed 2 lineages (A(H9N2) G1 and A(H9N2) Y280) as having at least some pandemic potential (see CDC IRAT SCORE).
All of which brings us to a new study, from researchers at several Provincial-level CCDC agencies, which looks at nearly 5,800 environmental samples from live poultry markets, farms, slaughterhouses, and bird habitats in Jiangsu Province in 2024, and finds further evidence of mammalian adaptation.
Given the detailed, and highly technical nature of much of this report, I've only posted the Abstract and some excerpts from the Discussion and Conclusion. Those looking for a deeper dive will want to follow the link to read it in its entirety, but the authors summed up their findings stating:They also compared 370 occupationally exposed human sera with 240 non-exposed sera using HI assays, and found a low level of seropositivity in both.
These findings confirm that Jiangsu’s circulating H9N2 viruses have acquired human receptor preference and mammalian adaptation, posing silent infection and pandemic risks
19 June 2026
Epidemiological and Virological Characteristics of H9N2 Avian Influenza Virus in Jiangsu Province, China, 2024Xue Gao 1,†, Huiyan Yu 2,†, Na Zhang 3, Liqi Liu 3, Jing Tong 1, Xian Qi 2, Haodi Huang 2, Shenjiao Wang 2, Zi Li 3,* … Liguo Zhu 2,*
AbstractH9N2 avian influenza viruses inherently carry cross-species transmission potential, making continuous surveillance critical for pandemic prevention. This study focused on monitoring the 2024 H9N2 epidemic in Jiangsu Province’s external environment, analyzing its molecular evolution and receptor binding properties, assessing cross-species transmission and pandemic risks, and investigating serological antibody levels across different human populations.
Environmental samples were collected from live poultry markets, farms, slaughterhouses, and bird habitats across Jiangsu, screened via quantitative PCR (qPCR), with positive samples used for virus isolation and whole-genome sequencing. Receptor binding properties were tested by hemagglutination assay, and H9N2 antibody levels were measured in 370 occupationally exposed individuals and 240 non-exposed individuals using hemagglutination inhibition (HI) assays.
Among the 5779 collected samples, 6.89% tested H9N2-positive, and 12 strains belonging to the Eurasian lineage Y280-like clade G57 genotype were successfully isolated. All strains carried the HA-Q226L mutation, with 11 showing preferential binding to human α-2,6 receptors and one strain possessing dual receptor binding capability.
Internal genes harbored mammalian adaptation mutations, and M2 proteins contained mutations conferring complete resistance to amantadine-class antiviral drugs.Serological tests revealed antibody positive rates of 4.05% in exposed populations and 2.5% in non-exposed populations, with no statistically significant difference between groups.
These findings confirm that Jiangsu’s circulating H9N2 viruses have acquired human receptor preference and mammalian adaptation, posing silent infection and pandemic risks. Enhanced surveillance and the development of candidate vaccine stockpiles are strongly recommended.
(SNIP)
Notably, dual receptor binding is a key determinant for cross-species transmission and pandemic potential in influenza viruses [21]. Strain CZ3053 not only possessed strong human receptor binding capacity but also retained agglutination activity against horse, sheep, and rabbit red blood cells. Analysis suggests that the HA-V306L mutation may be key for its acquisition of dual receptor binding capability. Amino acid substitution at position 306 may fine-tune the conformation of the receptor binding site through remote allosteric effects, enabling it to maintain avian α-2,3 receptor recognition capacity while further optimizing spatial adaptation to human α-2,6 receptors, thereby acquiring dual receptor binding characteristics.
All isolate PB2 proteins in this study carried a characteristic set of mutations (L89V, L134H, M147I, I292V, R340K, R389K, and A588V) [16]. Among these, M147I and R340K are key molecular markers of the G1-like lineage, closely related to enhanced polymerase activity and replication capacity in mammalian cells [22]. Additionally, combined with the commonly present mutations in PB1 protein (D622G) and PA protein (K356R, S409N, and A515T) related to virulence and polymerase activity, as well as adaptive mutations in NP protein that optimize nuclear transport efficiency (K398Q) and antagonize human restriction factor interference (V352M), these molecular characteristics functionally couple to provide a solid molecular basis for the H9N2 virus breaking through species barriers [23,24,25].
While trying to predict the source of the next influenza pandemic is a mug's game, H9N2 shows up twice the top 10 zoonotic influenza A viruses the CDC has pegged as having at least some pandemic potential, with the Y280 lineage having a higher emergence score than H5N1.Serological results showed low H9N2 exposure levels in human populations in Jiangsu region in 2024, with no statistically significant difference between occupationally exposed (4.05%) and non-occupationally exposed (2.5%) groups. Based on our findings, H9N2 infection risk may not be limited to occupationally exposed populations, as general residents may also face infection risks through live poultry market environmental exposure or aerosol contact.
Therefore, serological investigation and detection work should be strengthened for different populations. Meanwhile, both positive cases in the non-occupational group were from the adult group, possibly related to higher social activity frequency and environmental exposure opportunities in this age group. Since current antibody levels are far from sufficient to form population immune barriers, accelerating development and application of novel vaccines is a key measure for improving prevention and control effectiveness. 5.
Conclusions
H9N2 viruses circulating in Jiangsu Province in 2024 have acquired human receptor preference, along with PB2-A588V and other internal gene compensatory adaptations, indicating pandemic potential. It is recommended to conduct continuous surveillance of the H9N2 subtype AIV while accelerating candidate vaccine strain matching and stockpiling work for current circulating branches to respond to potential public health crises.
