Global distribution of H5 influenza viruses of different subclades in different continents.
#18,717
The immediate global reaction - just over a year ago - after the United States discovered a spillover of clade 2.3.4.4b H5N1 genotype B3.13 in dairy cattle, was that this was a fluke and unlikely to be duplicated outside of North America.
The April 2024 DEFRA Risk Assessment Of HPAI H5N1 Occurring in Cattle In the UK reassured:
The material detected has been sequenced and shown to belong to clade 2.3.4.4b strain B3.13, a viral reassortant between Eurasian High Pathogenicity Avian Influenza (HPAI) H5N1 and North American Low Pathogenicity Avian Influenza (LPAI) strains.
This strain has not been detected in the UK, and none of the viruses detected in the UK over the 2020 to 2024 HPAI outbreak period have contained genetic material originating from North or South American viruses.
Conventional wisdom was that cattle were not generally susceptible to influenza A infection - much less H5N1 - and therefore there had to be something `special' about the B3.13 genotype that permitted the spillover.
Despite the fact that researchers at Germany's FLI successfully infected four calves with an older clade of HPAI H5N1 (see EID Journal Experimental Infection of Cattle with HPAI H5N1) as far back as 2008 (see A Brief History Of Influenza A In Cattle/Ruminants).
Over the summer of 2024 the FLI successfully repeated their experiments with a contemporary European H5N1 virus, finding it replicated efficiently in bovine mammary tissue and could produce adaptive mutations (PB2 E627K) during replication
The reassuring assumption by the USDA that B3.13 entered dairy cattle via a single spillover from birds - and was subsequently only spread by the interstate transport of infected dairy cows - was challenged in early 2025 when another genotype (D1.1) turned up in dairy cattle in two states (Nevada & Arizona).
In March of 2025, the UK's Defra reported H5N1 Detected In Domestic Sheep with Mastitis, and over the past year we've seen reports of other non-B3.13 H5N1 in goats and sheep in Pakistan, horses in Mongolia, and pigs in Oregon.
Still, most countries conduct limited or zero testing of livestock for the virus, and even in the United States - where over 1,050 herds have tested positive - testing remains suboptimal, and the number of infected herds is likely significantly underreported (see Nature: A Mathematical Model of H5N1 Influenza Transmission in US Dairy Cattle).
All of which brings us to a new study, published yesterday in Emerging Microbes & Infections, where Chinese researchers experimentally infected bovine cells with locally sourced HPAI H5 viruses (non B3.13) and tested their lethality in mice.
This study used four H5N1 viruses (A/duck/Jiangsu/565/2024, A/duck/Henan/567/2024, A/duck/Shandong/571/2024, and A/goose/Hebei/584/2024) isolated from birds in live poultry markets (LPMs) in China in 2024, along with two H5N6 control viruses from 2021.
Although all H5N1 isolates exhibited efficient replication in bovine-derived MDBK cells, only 571/H5N1 strain demonstrated effective replication in MAC-T cells and displayed lethality (16.7%) in mice. But testing was of only a small subset of H5 viruses circulating in China.
While a limited survey of cattle in China turned up no evidence of spillover, they consider the risks to be genuine, and urge `enhanced surveillance of avian influenza viruses'.
This is a lengthy and detailed study, and well worth following the link to read in its entirety. I'll have a postscript after the break.
Emerging Microbes & Infections
Research ArticleJunlong Xiong,Shiping Ding,Jiangtao Zhou,Yunqi Cui,Xiaona Chen,Lihong Huang,show all
Accepted author version posted online: 12 May 2025
Abstract
In February 2024, H5N1 highly pathogenic avian influenza viruses (HPAIVs) of clade 2.3.4.4b were first reported in dairy cows in the USA. Subsequent multiple outbreaks on dairy farms and sporadic human infections have raised substantial public health concerns. In the same year, four H5N1 HPAIVs of clade 2.3.4.4b were isolated from ducks and geese in live poultry markets (LPMs) spanning seven provinces in China.
Evolutionary analysis demonstrated that these viruses had undergone two genetic reassortments with H5 influenza viruses from wild birds in different countries. Except for 565/H5N1, the other three viruses exhibited over 99% genetic homology with avian-origin H5N1 HPAIVs from South Korea and Japan.
Notably, 571/H5N1 demonstrated high replication efficiency in bovine-derived cells, particularly in bovine mammary epithelial (MAC-T) cells, and caused 16.7% (1/6) mortality in mice at a dose of 10⁵ EID₅₀/50 μL, indicating its zoonotic potential.
Given the potential cross-species transmission risk of H5N1 HPAIVs to cattle herds, we collected 228 serum samples from 12 cattle farms across five provinces and conducted serological testing to investigate seroprevalence of H5N1 HPAIVs in Chinese cattle herds. All tested samples were negative, indicating no widespread infection in the sampled cattle populations. However, infections in cattle from other regions cannot be ruled out. Nevertheless, due to the high mutability of H5N1 HPAIVs, enhanced surveillance of avian influenza viruses is critical to ensure timely responses to potential outbreaks.
(SNIP)
Conclusion
In summary, we isolated four H5N1 HPAIVs belonging to clade 2.3.4.4b from LPMs in China. The study revealed that all H5N1 isolates exhibited efficient replication in bovine-derived MDBK cells, but only 571/H5N1 strain demonstrated effective replication in MAC-T cells and displayed lethality (16.7%) in mice, which warrants high vigilance. Furthermore, testing of serum samples collected from multiple cattle farms across China showed all samples were negative. These results indicate that, within our detection scope, the currently circulating H5N1 HPAIVs in Chinese LPMs have not yet achieved widespread transmission in cattle populations.
While this study doesn't set klaxons blaring, there is enough here - along with other recent evidence - to suggest additional H5 spillovers are likely, and that we should be testing all types of livestock aggressively.
Sadly, most nations continue to follow a `Don't test, don't tell' strategy. What they don't detect, they don't have to deal with.
A strategy that may work well in the short run, but has a high potential for catastrophic failure over time.
