J. Inf.: Zoonotic Threat of Novel H6N2 Avian Influenza Virus with Internal Genes Exclusively Derived from H9N2, China, 2025

Transmission patterns between different hosts of  H6 viruses.

 
Credit: JOI: Prevalence and Transmission of Influenza A (H6) Viruses

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Last August, in JOI: Prevalence and Transmission of Influenza A (H6) Viruses Pose a Potential Threat to Public Health, we revisited the H6 family of influenza A viruses, which are endemic in Asian poultry and are believed to have some degree of zoonotic potential. 

H6N1 briefly made headlines in 2013 and 2014 after a college student in Taiwan was hospitalized with pneumonia (see Taiwan CDC: Epidemiological Analysis Of Human H6N1 Infection) and several dogs were found infected (see EID Journal: Influenza A(H6N1) In Dogs, Taiwan).

The CDC currently has this to say about H6 viruses: Avian Influenza A(H6) Viruses

LPAI A(H6) virus outbreaks in birds are not internationally reportable, therefore, its true prevalence is unknown. However, LPAI A(H6) viruses have been identified in various species of wild waterfowl and domestic poultry in Eurasia and the Americas. Known subtypes of A(H6) viruses include LPAI A(H6N1) and A(H6N2). In 2013, Taiwan reported the first known human infection with LPAI A(H6N1) virus.

While not a `reportable' disease, over the past several years we've seen growing interest by Chinese scientists over some of its recent evolutionary moves, including: 

Study: Influenza A (H6N6) Viruses Isolated from Chickens Replicate in Mice and Human lungs Without Prior Adaptation

Preprint: Progressive Adaptation of H6N1 Avian Influenza Virus in Taiwan Enhances Mammalian Infectivity, Pathogenicity and Transmissibility

That said, H6 viruses remain fairly far down our pandemic watch list, with H5N1 getting most of our attention, although it ranks 7th on the CDC IRAT List (see below).

In terms of likelihood of emergence, the CDC currently ranks a Chinese EA H1N1 `G4' swine virus at the very top of their list of zoonotic influenza A viruses with pandemic potential, with 2 other North American swine variant viruses and H9N2 scoring above H5N1.

While most (but not all) H9N2 infections have been relatively mild, it continues to evolve towards a more easily human transmissible virus (see EM&I: Enhanced Replication of a Contemporary Avian Influenza A H9N2 Virus in Human Respiratory Organoids).

H9N2 is also a highly promiscuous virus, which reassorts easily with other influenza A strains, and often lends its internal genes to more dangerous HA subtypes (see PNAS: Evolution Of H9N2 And It’s Effect On The Genesis Of H7N9).

All of which brings us to a new letter, published this week in the Journal of Infection, that reports on the detection and spread of a new H6N2 reassortment virus, which sports not only the NA gene from H9N2, but all 6 internal genes as well.

Although we haven't seen reports of human infection with this new reassortment (and the H6 HA retains avian characteristics), this wholesale replacement of 7 gene segments by H9N2 adds a number of known or suspected mammalian mutations to the mix. 

This new reassortant has been detected in poultry in several several provinces in eastern China at the end of 2025, suggesting it already well established. 

While none of this guarantees future greatness for this H6 reassortant, it is hard to imagine a better advantage, given H9N2's track record. I've just provided the link, and some excerpts from the correspondence. 

Click through to read the full report. I'll have a bit more after the break. 

Letter to the Editor

Zoonotic Threat of Novel H6N2 Avian Influenza Virus with Internal Genes Exclusively Derived from H9N2, China, 2025
 Kaituo Liu 1, Xiyue Wang 1, Jiehong Huang 1, Pan Liu, Yijia Sun, Wenhao Yang, Xiaolong Lu, Yu Chen, Jiao Hu, Min Gu, Xiaowen Liu, Shunlin Hu, Ruyi Gao, Xiaoquan Wang, Xiufan Liu

(EXCERPT)

In this study, we report the identification and characterization of a novel H6N2 reassortant virus isolated from poultry in Eastern China. Genetic analysis reveals that this virus possesses a hemagglutinin (HA) gene from circulating H6N6 waterfowl viruses, a neuraminidase (NA) gene from endemic poultry H9N2, and most critically, a complete set of six internal genes derived entirely from the H9N2 lineage, a genetic constellation known to potentiate cross-species infection8.

This represents the first natural detection of an H6N2 virus with an internal gene cassette exclusively derived from H9N2, and the virus has already achieved widespread circulation in in Eastern China (Jiangsu, Shandong, and Zhejiang provinces) poultry populations, indicating successful establishment.

The emergence of the novel H6N2 virus underscores the persistent and evolving threat posed by the co‑circulation of multiple subtype AIVs in China. Given that its molecular genetic profile indicates an elevated potential for cross‑species transmission, we strongly recommend that immediate enhanced and targeted surveillance, along with reinforced control measures in poultry and wild birds, should be implemented promptly to contain viral spread before human infections occur. 

(Continue. . . )

Admittedly, we've seen recent warnings from Chinese scientists on the spread of other, equally concerning, novel influenza A viruses, including last summer's Virology: Assessment of the Public Health Risk of Novel Reassortant H3N3 Avian Influenza Viruses That Emerged in Chickens).

While much of the news out of China is restricted, the impression is that both LPAI and HPAI viruses are spiralling out of control in Chinese poultry. 

Last November (see China MOA Announces New Guidelines to Expedite Animal Vaccine Strain Approvals ) China's MOA published a remarkable announcement - which tacitly admitted that many of their current animal vaccines (including against H9N2) were inadequate and/or suboptimal - and ordered major regulatory changes in order to accelerate updates.

This wasn't exactly a surprise, as previously, in NPJ Vaccines: Impact of Inactivated Vaccine on Transmission and Evolution of H9N2 Avian Influenza Virus in Chickens, we'd seen evidence that inactivated vaccines had failed to prevent - or even reduce - H9N2 in China's poultry, and they may have driven viral evolution (including mammalian adaptations).

While this report on H6N2 is concerning, it is part of a pattern we are seeing of increased diversity in avian influenza viruses circulating in China. While most of these reassortants are destined to fade into obscurity, it only takes one overachiever to put us back into pandemic mode. 

Stay tuned.