Credit USDA
#18,901
Nineteen months ago our view of avian influenza changed abruptly with the revelation that HPAI H5N1 had infected, and spread widely among, dairy herds across multiple U.S. states.
As we saw in A Brief History Of Influenza A In Cattle/Ruminants - despite some hints from the past - this caught most scientists completely by surprise.
Since this event was unprecedented outside of the laboratory, for the better part of a year we heard from official sources (USDA) that this was likely limited to the `bovine' B3.13 genotype, and was due to `a single spillover event' in Texas (which was further spread by the interstate shipping of infected cattle).
Almost immediately, only lactating dairy cows were considered `at risk', and cow-to-cow transmission was quickly hypothesized to be due to contaminated milking machines, although other routes of infection could not be ruled out (see EID Journal: Persistence of Influenza H5N1 and H1N1 Viruses in Unpasteurized Milk on Milking Unit Surfaces).
While initially reassuring, since then we've seen a long list of discoveries that have challenged many of those early assumptions about influenza A in ruminants, including:
- The detection of (1) HPAI H5 in goats and (2) alpacas in the United States, (3) serological evidence of HPAI exposure in goats and sheep in Pakistan, (4) the report last March UK's Defra reported H5N1 Detected In Domestic Sheep with Mastitis, and again in May; (5) serological evidence of H5N1 in sheep in Norway.
- The successful laboratory infection of cattle in Germany with other genotypes of H5N1 (see Germany: FLI Statement On Experimental Infection Of Dairy Cows With European H5N1 Virus).
- The USDA acknowledging last February the 2nd and 3rd spillover of another genotype - D1.1 - to cattle in two western states (see APHIS Statement On HPAI Genotype D.1 In Arizona Dairy Cattle.
- Last March (see Virology: Detection of Antibodies Against Influenza A Viruses in Cattle) a study showed bulls and steers were just as likely to carry antibodies to (non-HPAI H5) influenza A viruses as cows and heifers.
- And more recently, transmission studies which revealed - among other things - evidence of airborne transmission from exhaled cow breath (see Preprint: Surveillance on California Dairy Farms Reveals Multiple Sources of H5N1 Transmission).
Essentially they found that LPAI avian, swine and the 2009 H1N1pdm influenza A viruses all replicated efficiently in lab-grown bovine airway cells, demonstrating the potential for cattle to serve as `mixing vessels' or intermediate hosts in influenza's evolution and cross-species transmission
Efficient replication of avian, porcine and human influenza A viruses in well-differentiated bovine airway epithelial cells
Ang Su, Miaomiao Yan, Georg Herrler & Paul Becher
Article: 2572697 | Accepted author version posted online: 08 Oct 2025
https://doi.org/10.1080/22221751.2025.2572697
Abstract
We report that differentiated bovine airway epithelial cells are susceptible to avian, swine, and human influenza A viruses. This indicates that cows are a potential host of avian and mammalian influenza A viruses and may be implicated in the transmission of influenza viruses to other animal species and humans.
(SNIP)
The major aim of this study was to investigate the susceptibility of differentiated bovine airway epithelial cells (BAEC) to avian and mammalian IAVs, and to analyze their effects on BAEC.Two LPAIV strains, H7N7 (A/duck/Potsdam/15/80) and H9N2 (A/chicken/Saudi Arabia/CP7/98), swine influenza virus (SIV) strain H1N1 (A/sw/Bad Griesbach/IDT5604/2006), and the human pandemic 2009 IAV strain H1N1 A/Germany/1580/2009 (HA H1N1(pdm09) were analyzed10,11.
Discussion
The analysis of the amount of released infectious virus and the number of foci formed on ciliated cell layers demonstrated significant differences in susceptibility to the individual influenza viruses used in this study.
Avian influenza viruses in general prefer the α2,3-linked sialic acid (SA) as their receptor determinant12. However, the AIV H9N2 virus used here had been shown by glycan array analysis to recognize both α2,3- and α2,6-linked SAs as receptor determinant11. It might be surprising that AIV H9N2 replicated significantly less efficient (100-fold) compared with AIV H7N7, as both α2,3- and α2,6-linked SAs can be detected in the bovine respiratory tract13.
Mucins, which may hamper the spread of infection and have to be inactivated by appropriate viral neuraminidases14, post-entry steps15, and differences in the response of the innate immune system to different virus strains may also result in different replication efficiencies of AIV H7N7 and AIV H9N2.
Only mild respiratory signs have been reported in many affected dairy cattle herds in the US9. These characteristics can be explained by limited spread of influenza A viruses in the bovine respiratory tract, which correlated with the rapid recovery ability of bovine airway cells.
Future investigations will extend the application of this model to other influenza viruses, including avian and bovine HPAIV H5N1, or assess whether human-derived airway epithelial cells display comparable strain-specific differences in virulence.
While it seems incredible that after > 18 months, we don't have a better grasp on HPAI H5's (and other influenza A viruses) impact on livestock, surveillance and testing of cattle, swine, and other livestock remains limited in the United States and around the world.
As we've seen (see EID Journal: Avian Influenza A(H5N1) Virus among Dairy Cattle, Texas, USA) many farmers have been less than receptive to the idea, fearing the stigma and financial losses from having an `infected' herd.
As a result, `Don't Test, Don't Tell' remains an attractive option, particularly when livestock display relatively minor, manageable, or temporary symptoms.
The FAO recommends countries establish `robust passive surveillance', but that is predicated on the idea that farmers will recognize an infection, call in a veterinarian who will do appropriate testing, and they will report it to state authorities (who will then openly share it).
Whether the spread of influenza A viruses in cattle will ever lead to dangerous reassortments or mammalian adaptations, remains to be seen. All of this could end up being more of academic interest than an imminent public health threat.
But without far better surveillance, testing, and the sharing of data - if something untoward does emerge - odds are we'll never see it coming.
