#18,927
In October of last year we saw multiple reports of captive tigers in Vietnam dying from HPAI H5N1 (see Vietnam: Govt. Confirmation Of `Dozens' Of Tiger Deaths (H5N1 Suspected), a pattern we've seen repeated a number of times, including 2016's Fatal H5N1 Infection In Tigers By Different Reassortant Viruses - China.
Typically, tigers (and other captive carnivores) are infected via consumption of raw poultry, which is often a mainstay of their diet.
Yesterday the journal Emerging Microbes and Infections published a Research Letter on this event, which reveals the H5N1 clade involved to be 2.3.2.1e - the same as has been linked to recent human infections in Cambodia.
Unlike H5N1 cases reported in the United States - which are due to a milder clade 2.3.4.4b - recent Cambodian cases have been caused by a new reassortment of an older clade of the H5N1 virus (recently renamed 2.3.2.1e) - which appears to be spreading rapidly through both wild birds and local poultry.
The authors describe finding several mutations of note, including the PB2-E627K mammalian adaptation, as well as HA-N158D and HA-T160A which can enhance transmissibility.
This is an early release of an accepted manuscript, and the finalized (and edited) version of the PDF will be published at a later date.
I've posted the link, abstract, and a brief excerpt below. Follow the link to read the report in its entirety. I'll have a brief postscript after the break.
Research Letter
Murasaki Amano,Nguyen Thi Nga,Nguyen Le Khanh Hang,Nguyen Dang Tho,Nguyen Thi Diep,Dam Thi Vui, show all
Article: 2582252 | Accepted author version posted online: 28 Oct 2025
Cite this article https://doi.org/10.1080/22221751.2025.2582252
Abstract
Recently, infections with the H5N1 subtype of highly pathogenic avian influenza virus (H5N1-HPAIV) in mammals have been reported worldwide, including in cows in the United States and successive human cases in Cambodia. In Vietnam, 47 tigers and three leopards died from H5N1-HPAIV infection between August and October 2024. This study aimed to determine the origin of the H5N1 strains that infect tigers in Vietnam and to identify specific mutations associated with mammalian infection.
Specimens were collected from tigers that died of suspected H5N1-HPAIV infection in southern Vietnam in September–October 2024. RNA was extracted and subjected to whole-genome sequencing. Time-stamped phylogenetic analysis was performed using H5N1 sequences recently detected in Vietnam and neighbouring countries. Phylogenetic results revealed that the strain found in tigers (Tiger H5N1 strain) belonged to clade 2.3.2.1e and was genetically close to the H5N1-HPAIV lineage responsible for ongoing human infections in Cambodia since 2023.
Tiger H5N1 strains harboured several amino acid substitutions associated with mammalian host adaptation or transmissibility, such as E627 K in polymerase basic protein 2, similar to the Cambodian human H5N1 strains. This mammalian-adapted H5N1 lineage should be continuously monitored in poultry and mammals, including humans, in Vietnam to prevent further transmission.
(SNIP)
The most recent report investigating the lineage and distribution of the H5N1 influenza virus in Vietnam was published in 2019 [14]. This report indicated that clade 2.3.2.1 was distributed in central and southern Vietnam, while clade 2.3.4.4 was predominantly found in northern Vietnam [14].
However, since 2020, clade 2.3.4.4b has rapidly spread worldwide, resulting in avian influenza outbreaks reported in 84 countries between 2022 and 2023 [15]. In Vietnam, clade 2.3.4.4b has also expanded nationwide since 2020, and as of 2025, clade 2.3.4.4b has become the majority within the country (Supplementary Figure S2).
At present, clades 2.3.2.1e and 2.3.4.4b are found in the same geographical area in southern Vietnam.
Notably, the identification of clade 2.3.2.1e viruses with mammalian adaptation potential in this study has given rise to concerns regarding the acquisition of mammalian adaptation capacity through genetic reassortment. Acquisition of mammalian adaptation capacity by a highly infectious lineage such as clade 2.3.4.4b could potentially trigger the next pandemic. Consequently, it should be essential to carefully monitor the emergence of reassortants in Vietnam over the forthcoming decade.Influenza viruses evolve primarily through abrupt reassortment and much slower antigenic drift. Eighteen months ago we learned that this older 2.3.2.1 c clade had reassorted with the newer clade 2.3.4.4b virus in late 2023.
This new reassortment was recently reclassified as clade 2.3.2.1e (see WHO: Influenza at the Human-Animal Interface Report - Identifies New H5 Clade 2.3.2.1e Infections in Cambodia & Vietnam).
While a clade 2.3.4.4b virus could eventually pick up these mutations on its own, another reassortment event could provide it with a convenient shortcut, boosting its pandemic potential.
Conversely, clade 2.3.2.1e could continue to expand its geographic range - as have other H5 clades - and present an enhanced threat of its own.
As much as we'd like to think of HPAI H5 as a single threat, the reality is there are hundreds of genotypes, numerous subtypes (H5N1, H5N2, H5N5, H5N6, etc.), and a handful of active clades in circulation around the globe.
While the odds are long that any one will become a pandemic strain, each is embarked on its own evolutionary path.
And it only takes one to get `lucky' in order to plunge the world back into another global health crisis.
