In terms of risk of emergence, the H9N2
Y280 lineage is ranked higher than H5N1
#19,194
While LPAI H9N2 may not be the most headline grabbing avian flu virus, it is quite likely the most versatile. It is highly promiscuous, reassorting easily with many other subtypes (including H5Nx and H7Nx), it has diverged into numerous clades, and it continues to accrue mammalian adaptations.
While testing and reporting of cases around the globe is limited, over the past 12 months more than 2 dozen human cases have been reported (see FluTrackers H9N2 case list).
As a result, H9N2 gets more than a little attention by researchers.
- Last month, in Preprint: Outbreak of H9N2 Avian Influenza Viruses in Lesser Rhea in Peru, June-July 2025, we learned of a newly identified - and highly virulent - South American strain of H9N2.
- Also last month, in Eurosurveillance: Cross-reactive human antibody responses to H9N2 influenza virus, New York, United States, 2025, we saw that ` pre-existing immunity to H9N2 in humans that is dominated by cross-reactive but largely non-neutralising antibodies, with a greater contribution from NA-directed responses.'
- Last October, in China CDC Weekly: Epidemiological and Genetic Characterization of Three H9N2 Viruses Causing Human Infections, investigators reported a number of indicators of increased mammalian adaptation within the virus, including an enhanced ability to infect upper respiratory (α2,6-sialic acid) tract receptors, and a number of HA protein mutations, including; H191N, A198V, Q226L, and Q234L.
- The Asian Y280/G57 lineages have shown increasing signs of mammalian adaptation (see EM&I: Enhanced Replication of a Contemporary Avian Influenza A H9N2 Virus in Human Respiratory Organoids)), while the African and Middle Eastern Lineages (mostly European G1-like) are older and less evolved.
All of which brings us to a new report, published last week in Emerging Microbes & Infections, which describes a new clade of LPAI H9N2 recently discovered in Laos.
A new clade of H9N2 avian influenza virus circulating in Laos
Jiaming Li ,Chunge Zhang ,Ren Li ,Yanqing Wang ,Rahat Ullah Khan ,Ruichang QuanArticle: 2678641 | Received 05 Feb 2026, Accepted 19 May 2026, Published online: 04 Jun 2026
https://doi.org/10.1080/22221751.2026.2678641ABSTRACT
In 2024, we identified and sequenced 52 avian influenza A (H9N2) virus strains in Laos. Using the established H9N2 genomic classification system, a novel HA gene clade of the A/chicken/Beijing/1/94-like (BJ/94-like) lineage, designated Clade 4.6.20, was identified.
This new clade is phylogenetically distinct from the previously described clades, and the representative strains in this new Clade 4.6.20 presented a low cross reactivity to the antisera of other clades, suggesting antigenic drift of the viruses between the new Clade 4.6.20, and other clades in the dominant lineage of Clade 4.6.
In addition, all the newly identified viruses in Clade 4.6.20 possessed HA-L226 and NP-N52 mutations, which are associated with human-type receptor binding and human MxA-related innate immunity escape, respectively.
Our findings underscore the necessity of global surveillance network and cooperation to monitor the evolution of AIVs, update vaccine seed strains, and develop new vaccines with high effectiveness against H9N2 AIVs circulating globally, which threaten poultry and human health.
(SNIP)
In conclusion, the identification of a novel H9N2 clade (Clade 4.6.20) in Laos suggests that influenza viruses including both avian and human viruses may undergo undetected evolutionary changes in regions with inadequate surveillance, posing significant public health threats. This highlights the need to enhance international collaboration, improve surveillance systems, and develop new vaccines and NPIs to mitigate the increasing risks associated with cross-border viral spread and zoonotic transmission.
This is the second `novel' LPAI H9N2 virus discovery reported in less than a month, and it comes just a couple of months after Europe's first imported H9N2 case (from West Africa).
While primarily an avian virus, LPAI H9N2 has a track record of also infecting humans, pigs, and even bats (see Preprint: The Bat-borne Influenza A Virus H9N2 Exhibits a Set of Unexpected Pre-pandemic Features).China's attempts to control this rapidly evolving H9N2 virus with poultry vaccines have proved disappointing (see J. Virus Erad.: Ineffective Control Of LPAI H9N2 By Inactivated Poultry Vaccines - China).
And last year, in NPJ Vaccines: Impact of Inactivated Vaccine on Transmission and Evolution of H9N2 Avian Influenza Virus in Chickens, we saw evidence that not only had inactivated vaccines failed to prevent - or even reduce - H9N2 in China's poultry, they may have driven viral evolution (including mammalian adaptations).
Despite all of this - because it is not a high-risk H5 or H7 avian virus - H9N2 remains a `non-reportable' disease in poultry (see Terrestrial Animal Code Article 10.4.1.), allowing much of its spread and evolution to fly under the radar.
Hopefully these recent reports will spur additional surveillance, because - contrary to popular belief - what we don't know can hurt us.
