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Beyond that, there are other subclades of the HPAI H5 virus circulating in places like Cambodia, Bangladesh, and India (see 2025's WHO: Influenza at the Human-Animal Interface Report - Identifies New H5 Clade 2.3.2.1e Infections in Cambodia & Vietnam).
Simply put, the H5Nx virus currently infecting cattle and humans in Washington state is closely related to - but genetically distinct from - numerous H5 viruses circulating in Europe, Australia, or South Korea.
Since 2022 more than 100 different genotypes have been identified in the United States alone. Some are more pathogenic in birds or mammals - while others are more benign - but more are expected to emerge over time.
Most of these variants are destined to become evolutionary failures; ultimately unable to compete with more biologically `fit' variants already in circulation.
Over the past 20+ years we've seen hundreds of them appear - sometimes only briefly - before fading away. Occasionally, however, a new variant will bring something new to the party.
In early 2014 an emerging H5N8 virus in South Korea improved its ability to be carried long distances by migratory birds. In less than a year it had crossed the Pacific and sparked the first major North American epizootic with HPAI H5, and the following year (2016) conquered Europe.

In 2021 a new and improved H5N1 emerged in Europe and quickly supplanted H5N8, winging its way first to North America, then South America, and then the Antarctic. In 2026, it reached Australia and New Zealand.
This new H5N1 has shown an increased affinity for infecting mammals, and a much wider avian host range (see DEFRA: The Unprecedented `Order Shift' In Wild Bird H5N1 Positives In Europe & The UK).
Since then, we've seen HPAI H5 increase its ability to infect dairy cattle, sheep, goats, and other ruminants, even as it continues to occasionally spill over into humans.
Although H5's evolutionary trajectory is both erratic and unpredictable, as long as they circulate, these avian influenza viruses will undoubtedly continue to reinvent themselves.
All of which bring us to a new research article, published yesterday (Nov 5th) in Emerging Microbes & Infections, which describes the detection of an antigenically distinct cluster of HPAI H5 viruses which appeared in China in 2024-2025 (see distance map at top of blog).
While the authors didn't report any immediately alarming red-flags (e.g. increased virulence or transmissibility, mammalian markers, etc.), this is a reminder that HPAI H5 viruses continues to evolve, and what we say about their threat today may not hold true tomorrow.
Much of this report is highly technical, and of interest primarily to virologists. Those desiring a deeper dive will want to follow the link to read it in its entirety.
Research Article
Xinkui Zhang ,Yujia Yang , Xirong Huang, Shunyin Fang ,Xinyu Han ,Dandan Wei , show all
Article: 2760125 | Accepted author version posted online: 05 Nov 2026
Cite this article https://doi.org/10.1080/22221751.2026.2760125Abstract
Clade 2.3.4.4b H5 viruses have undergone continuous evolution since their emergence in China, but the extent of genetic and antigenic diversification among recently circulating viruses remains unclear.
Here, we characterised 18 H5 viruses isolated through routine surveillance in China during 2024-2025, together with publicly available clade 2.3.4.4b H5 sequences collected since 2020.
Phylogenetic analysis revealed that these isolates formed a distinct evolutionary cluster within clade 2.3.4.4b, designated the G2-derived emerging cluster (G2-EC), which emerged around mid-2024 and exhibited clear genetic divergence from previously circulating H5N1 viruses.
G2-EC viruses accumulated a characteristic set of hemagglutinin amino acid substitutions, most of which were located in antigenic regions. Across the clade 2.3.4.4b H5 virus population, the estimated mean HA evolutionary rate was higher during 2024-2025 than during preceding periods.
These genetic changes were accompanied by marked antigenic divergence from the Re14 vaccine strain, with 4- to 32-fold reductions in HI titres. Genomic analysis revealed acquisition of PB1 segment from a distinct genetic background in G2-EC H5N1 viruses, followed by the emergence of H5N6 viruses sharing a highly similar genetic backbone but carrying a distinct NA segment, indicating sequential reassortment.
Animal experiments showed that representative G2-EC viruses retained high pathogenicity and efficient direct-contact transmission in SPF chickens, while exhibiting relatively limited lethality in mice. Collectively, these findings document a recent evolutionary transition of clade 2.3.4.4b H5 viruses in China, characterised by genetic and antigenic divergence accompanied by sequential reassortment, underscoring the need for continued genomic and antigenic surveillance.
(SNIP)
Evolutionary rate analysis further suggested that the estimated mean evolutionary rate of the HA gene of clade 2.3.4.4b H5 viruses was higher during 2024–2025 than during the preceding two periods. Together with the emergence of the new evolutionary cluster and the accumulation of multiple characteristic substitutions in its HA protein, this observation suggests that 2024–2025 may represent an important phase of enhanced genetic divergence within the clade 2.3.4.4b H5 virus population in China.
However, the number of HA sequences available for evolutionary rate estimation during this period was relatively limited, which may have increased uncertainty in the posterior estimates and resulted in partial overlap of the 95% HPD intervals among different periods. Therefore, although the estimated mean evolutionary rate was higher during this period, this trend still requires further validation using larger-scale surveillance datasets.(Continue . . . )
Whether we are seeing the start of a new (and potentially important) branch in HPAI H5Nx's evolution - or simply a flash in the pan - is hard to say. This study is based on just 18 sequenced viruses (15 H5N1, 3 H5N6) acquired from routine surveillance in China.
To date, viruses belonging to this cluster have been detected predominantly in China. Apart from a small number of highly similar sequences identified in environmental samples from Japan in November 2025, no evidence of widespread detection of G2-EC-related viruses has been observed among publicly available H5N1 virus sequences from other countries or regions.
Limited surveillance, along with delays in depositing sequences (see Nature: Lengthy Delays in H5N1 Genome Submissions to GISAID), mean that we are only catching glimpses of H5's evolution.
Which is why we should be prepared for surprises going forward.







