Monday, May 25, 2026

Virulence: Surveillance and biological characterization of H3 subtype avian influenza viruses in Eastern China


Credit ECDC

#19,176

Over the past few years we've seen a noticeable uptick in interest by Chinese researchers into H3 virus evolution, particularly in Eastern China's poultry. While perhaps not as alarming as H5N1, H3 viruses have a long history of spilling over into humans and causing pandemics (see graphic above). 

The avian H3N2 pandemic virus emerged in 1968, and while it killed somewhere between 1-4 million people during the pandemic, it has killed many times more than that over the past 56+ years.  

A little over 20 years ago (2004) an equine H3N8 virus jumped to dogs in Florida, before spreading globally. Three years later, an avian H3N2 virus in South Korea, followed suit, with both reassorting with other subtypes (see J. Virology: Zoonotic Risk, Pathogenesis, and Transmission of Canine H3N2).

In 2011 avian H3N8 was found in marine mammals (harbor seals), and 2012’s mBio: A Mammalian Adapted H3N8 In Seals, provided evidence that this virus had recently adapted to bind to alpha 2,6 receptor cells, the type found in the human upper respiratory tract.
In 2015's J.Virol.: Experimental Infectivity Of H3N8 In Swine, we saw a study that found that avian (but not canine or equine) H3N8 could easily infect pigs. 
All worrisome signals, but it was the 2022 emergence of a zoonotic H3N8 virus in China - first infecting 2 children 400 km apart in Henan and Hunan Provinces in April and May of 2022 - and more recently a fatal infection of a 56 year old woman in Guangdong Province, that really raised concerns. 

This led to 2023's EID Journal: Evolution of Avian Influenza Virus (H3) with Spillover into Humans, China, where researchers described finding 4 sub-lineages and an astonishing 126 genotypes of avian H3 viruses circulating in China.  

The authors also described a recent reassortment event where H3N8 acquired the internal genes from LPAI H9N2, a promiscuous virus which had previously contributed genes to both H5N1 and H7N9 (see PNAS: Evolution Of H9N2 And It’s Effect On The Genesis Of H7N9).
Since then, we've looked at a number of cautionary reports on H3 viruses from China, including:
ABSTRACT

H3 subtype avian influenza viruses (AIVs) are frequently detected in poultry and wild birds, however, systematic characterization of contemporary isolates remains limited. We aimed to investigate the genetic evolution, pathogenicity, and transmission characteristics of H3 subtype AIVs circulating in Eastern China.

Seven H3 subtype AIVs isolated between 2014 and 2021, including five H3N2, one H3N3, and one H3N6 strain, were analyzed. Phylogenetic analysis showed that all isolates belonged to the Eurasian lineage. Evidence of extensive reassortment with other AIV subtypes, as well as adaptive mutations associated with pathogenicity, and cross-species transmission, particularly in H3N2 subtype AIVs, was identified.

Notably, H3N2 subtype AIVs exhibited dual receptor-binding properties, recognizing both SA α-2,3-Gal and SA α-2,6-Gal receptors. Although all isolates demonstrated low pathogenicity in chickens, mice, and guinea pigs, variations in transmission efficiency were observed.

The H3N2 strain A/Duck/Anhui/LY/2021 showed the highest capacity for cross-species and aerosol transmission among guinea pigs. Overall, these findings indicate that H3 subtype AIVs have the potential for cross-species transmission and highlight the importance of continued surveillance of H3 subtype AIVs circulating in nature.

(SNIP)

Discussion
In April 2022, the first human infection with the H3N8 virus was reported in Henan Province, China [Citation50]. In May 2022, a second case was identified in a 5-year-old boy in Hunan Province, China [Citation16]. These events have raised substantial concerns regarding the potential public health impact of emerging H3N8 subtype AIVs. In addition to H3N8 subtype AIVs, H3N2 subtype AIVs are continuously detected in poultry throughout the year in southern China, according to epidemiological surveys [Citation51].
Previous studies have demonstrated that H3N2 subtype AIVs can be transmitted between guinea pigs and ferrets via respiratory droplets [Citation2]. Furthermore, recent isolates have acquired mutations associated with increased binding affinity for human-type receptors and enhanced transmissibility in ferrets, posing a potential risk to human health [Citation52].
In China, H3N2 subtype AIVs are widely detected in LPMs [Citation44], increasing the likelihood of cross-species transmission from avians to mammals. Therefore, the cross-species transmission potential of H3N2 subtype AIVs, particularly from avians to mammals, warrants close attention. Phylogenetic analysis in this study showed that all seven H3 subtype AIVs belong to the Eurasian lineage, within which multiple cross-species transmission events have historically occurred. Notably, H3N2 subtype AIVs (LY strain), presented potential cross-species transmission characteristics from avians to mammals, which should be more attention.

(SNIP)
In conclusion, H3N2 subtype AIV, particularly the LY strain exhibited both interspecies and cross-species transmission characteristics, suggesting an increased potential for transmission from avian to mammalian hosts.
These findings imply that continued surveillance of H3N2 AIVs in LPMs is critical, as they may pose an emerging concern to public health, and monitoring key molecular markers associated with mammalian adaptation could help in predicting and preventing future cross-species transmission events [Citation59].

        (Continue . . . )

Although the authors present no evidence of an immediate threat, H3 viruses have a proven pandemic track record, and we continue to see signs of a shift towards dual receptor-binding properties (avian & mamamallian) which should be viewed as concerning. 

While there are many routes to the next pandemic (and not all of them involve novel influenza), twice in my lifetime an avian flu virus has emerged as a pandemic strain (H2N2 in 1957 and H3N2 in 1968). 

A third flu pandemic (H1N1) emerged from swine in 2009, and currently 4 of the top 10 emerging zoonotic threats on the CDC's IRAT list are swine-variant viruses, with China's Avian-like H1N1 swine flu virus at the top of the list.

And as we've discussed often over the past few years (see Are Influenza Pandemic Viruses Members Of An Exclusive Club?), the progression of human influenza pandemics over the past 130 years has been H2, H3, H1, H2, H3, H1, H1. 

Which suggests that - while an H5, H7, H9, or even H10 pandemic is always possible - the odds probably favor seeing an an avian, swine, or canine emerging H1, H2, or H3 virus as our next pandemic threat. 

Which is why we follow research papers like today's with particular interest. 

Posted by at