Cats As Potential Vectors/Mixing Vessels for Novel Flu
#18,835
While we enjoy the relative lull in HPAI reports during the summer months, the annual southbound migration of birds from their high latitude roosting sites has already begun, and with it may soon arrive new genotypes, subtypes, and variants of HPAI H5.
In North America alone, more than 100 genotypes have been identified over the past 3+ years, with more expected to emerge over time. Over the past 16 months we've seen 4 new genotypes of note emerge in the United States.- B3.13 aka the `bovine' strain affecting dairy cattle in at least 17 states and mildly infecting dozens of humans, along with > 100 cats.
- D1.1 a wild bird/poultry strain which has spilled over into > a dozen people in Washington State, severely infected a teenager in British Columbia, and produced a fatal infection in Louisiana.
- D1.2 a wild bird/poultry strain which recently detected in poultry and 2 pigs in Oregon
- D1.3 a recently detected wild bird/poultry strain which has been infection poultry and at least 1 human
In Cambodia we've seen a reassorted clade 2.3.2.1e virus infect > 30 people since 2023, while a new triple-reassortant H5N1 clade 2.3.2.1a virus in India has reportedly infected both humans and cats.
Other HPAI H5 genotypes/subtypes have infected cats, dogs, (and other mammals) in Europe and Asia (see here, here, here, and here), and North America. The USDA lists at least 144 domestic cats infected, along with dozens of other felines.
The take-away here is that HPAI H5 has diversified into numerous new subclades, subtypes, and genotypes; with many of them demonstrating an affinity for infecting both terrestrial and marine mammals.
While not unheard of before 2020 (see 2015's HPAI H5: Catch As Cats Can), we've seen a significant increase in the number of HPAI spillovers into mammals, and cats appear to be particularly susceptible.
These trends (and more) have led veterinarians to worry that companion animals (particularly cats, but also including dogs, ferrets, mice, etc.) could serve as a potential `mixing vessel' for reassortment, or as a bridge to infecting humans.
A few past blogs include:
Emerg. Microbes & Inf.: Marked Neurotropism and Potential Adaptation of H5N1 Clade 2.3.4.4.b Virus in Naturally Infected Domestic Cats
All of which brings us to a new open access article published in the Journal of American Veterinary Association last week, which looks at the concerns over the role of companion animals in the evolution and spread of HPAI H5.
Due to its length I've only posted the abstract and some extended excerpts. You'll want to follow the link to read it in its entirety.
I'll have a brief postscript after you return.
Companion animals and H5N1 highly pathogenic avian influenza: cause for concern?
Jane E. Sykes BVSc, PhD, MPH, MBA, DACVIM jesykes@ucdavis.edu
Open accessPublished online August 8, 2025doi.org/10.2460/javma.25.06.0388
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Abstract
The first known human infection with a highly pathogenic H5N1 influenza A virus appeared in China in 1997. Between 2003 and 2017, the WHO documented an additional 862 human cases, mainly from southeast Asia and Egypt, with a mean annual case fatality rate of 56%. By 2006, the susceptibility of cats to severe respiratory and neurologic disease became apparent.Scientists raised concerns regarding the potential for domestic cats to transmit novel pathogenic strains to humans. But after 2006, reports of new H5N1 infections in companion animals dwindled, and human cases fell after 2016.In 2021, H5N1 clade 2.3.4.4b viruses suddenly appeared in Europe and spread rapidly to the Americas, wreaking havoc on wildlife and crippling the poultry and dairy industries. Between 2022 and 2025, dozens of domestic cats died, most often following raw food consumption. Unease regarding the transmission potential of pets resurfaced.Although most human infections in the Americas were mild and associated with poultry or dairy contact, the recent detection of genotype D1.1 in association with severe illness or death is cause for concern. Genotype D1.1 has now also been detected in dairy cattle and domestic cats. Reports of H5N1 clade 2.3.2.1a viruses in India suggest a new potential threat.Successful control of H5N1 infections is strongly dependent on a One Health approach. Small animal veterinarians play a key role in this approach through recognition of cases and education of pet owners, thus preserving the human-animal bond.
(SNIP)
Risk of Human Infection from Domestic Cat Exposure
At the time of publication, the risk of severe human infection because of pet exposure is considered low. However, the ability of H5N1 clade 2.3.4.4b strains to replicate in such a broad array of avian and mammalian host species—together with the frequency of reassortment events—creates a recipe for emergence of strains with greater pathogenicity for humans.
Factors that support the ability of cats to act as vessels for reassortment of mammalian and avian influenza virus subtypes include (1) widespread tissue distribution of both α-2,3-Gal and α-2,6-Gal sialic acid receptors in cats,97 (2) co-localization of H5N1 antigen with these receptors,15 and (3) recovery of viruses from infected cats that have mutations associated with adaptation for replication in mammals.61
The widespread distribution of pet cats, their close proximity with humans, their predatory behavior and outdoor roaming activity, and the popularity of raw food diets add to the potential for infection and spillback.
Further, although clade 2.3.4.4b viruses have predominated worldwide, other clade 2 H5N1 viruses have caused severe human infections in south Asia (Bangladesh and India, clade 2.3.2.1a) and southeast Asia (clade 2.3.2.1c) since 2022.98 In March 2024, an H5N1 clade 2.3.2.1a virus was detected in a severely ill child returning home to Australia from India.98 In January 2025, a closely related H5N1 clade 2.3.2.1a virus was detected in 2 cats that died in India.99
(SNIP)
Conclusion
The emergence of H5N1 clade 2.3.4.4b strains in 2021 represented a more significant threat than previous reports of fatal H5N1 AIV infections in cats from Europe, the Middle East, and Asia.
Compared to previous H5N1 variants, clade 2.3.4.4b strains have demonstrated more rapid global dissemination, more frequent reassortment with LPAIVs, a greater ability to replicate in an enormous variety of mammalian species, and a wider array of transmission pathways to domestic cats.
The recent detections of genotype D1.1 in 3 humans with severe or fatal illness from Canada, the US, and Mexico and in a cat from the US in early 2025 are worrisome new developments. Concurrently, the recognition of highly related clade 2.3.2.1a viruses in humans and cats from India demonstrates how multiple pathways for reassortment could evolve simultaneously.
Veterinarians play important roles in educating owners regarding ways to prevent infections in pets. More studies of the prevalence of persistent subclinical infections in dogs and cats are needed, as these also represent a threat to human and animal health. In light of the general availability of safer vaccines for cats, interdisciplinary conversations are warranted regarding the feasibility, impact, and value of immunizing cats against H5N1 infections.
The HPAI H5 threat of today is far different from what it was 20, 10, or even 5 years ago. There is far greater viral diversity (subclades, genotypes, subtypes) circulating today than we've ever seen before.
While it is possible that H5Nx faces some insurmountable species barrier (see Are Influenza Pandemic Viruses Members Of An Exclusive Club?), it continues to expand its (avian & mammalian) host range around the globe.
Our understanding of the ecology of H5 - in the wild, on the farm, and in companion animals - remains limited, and we see the continued introduction of new genotypes and variants every year.
Yet most people seem oblivious to the threat (see Two Surveys (UK & U.S.) Illustrating The Public's Lack of Concern Over Avian Flu), and many governments are content to do little and say even less.
We humans like to believe that tomorrow will be pretty much like today, or yesterday (aka `Normalcy Bias '). We tend to discount bad things happening in the future in favor of enjoying more immediate rewards.
So we blithely build cities on known fault lines or in the shadow of a volcano, or subdivisions and schools on toxic waste sites, and hope for the best. Similarly, we seem to be waiting for HPAI to `burn itself out' in cattle, or in wild birds; because it is easier than actually addressing the threat.
These laissez-faire style strategies can often work well for years, sometimes even decades.
But when they fail, they have a habit of doing so spectacularly.
