#19,107
Over the past 2 years we've seen 2 new genotypes of H5N1 emerge in North America - `Bovine' B3.13 and D1.1 - both of which have infected thousands of cattle, dozens of humans, and a huge (and largely uncounted) number of birds.
While neither of these viruses have evolved into an easily transmissible strain, both have shown evidence of mammalian adaptation.
Human cases have ranged from mild or asymptomatic (see JAMA Open: Asymptomatic Human Infections With Avian Influenza A(H5N1) Virus Confirmed by Molecular and Serologic Testing) to severe and even fatal (see Louisiana Department of Health Announces 1st H5N1-related Fatality).
Recent studies and preprints (using a variety of lung explant cultures, lung organoids, and human nasal epithelial cells) have found these new genotypes appear to be better adapted to the human respiratory system than older strains.
A few recent examples include:
Preprint: Bovine-derived Influenza A virus (H5N1) Shows Efficient Replication in Well-differentiated Human Nasal Epithelial Cells Without Requiring Genetic Adaptation
J.I.D.: Avian influenza virus A(H5N1) genotype D1.1 is better adapted to human nasal and airway organoids than genotype B3.13
Pre-Print: A Cattle-derived Human H5N1 Isolate Suppresses Innate Immunity Despite Efficient Replication in Human Respiratory Organoids
While these studies utilize different methods and materials, they have constantly painted a picture of the recent emergence of a more `mammalian adapted' HPAI H5 viruses.
To that list we can add a dispatch, published this week in the EID Journal by researchers from the University of Hong Kong and St. Jude Children's Hospital, which looks at two cattle derived H5 strains (from Ohio & TX) of the B3.13 genotype in human bronchus and lung ex vivo explants.
While today's study doesn't explicitly test the D1.1 genotype, they make note of previous studies (see above) which suggest - in some ways - it may be even better adapted than B3.13.
While relatively brief, much of this dispatch is technical in nature, and those with a keen interest will want to read it in its entirety.
This study compares B3.13 to 3 other viruses; a Clade 0 H5N1 virus (Hong Kong 1997), an aggressive H5N6 isolate from China (2014), and a 2009 H1N1 virus from Hong Kong. Briefly, they report:
- Bovine H5N1 genotype B3.13 shows partial adaptation to human respiratory tissue.
- B3.13 replicates in lung tissue on par with the 2009 H1N1pdm virus, albeit lower in the bronchus than either H1N1pdm and H5N6.
- Receptor binding tests suggest better adaptation to α(2–6)-linked SA, compared to the early H5N1 virus.
- B3.13 induced proinflammatory responses, but far less than avian H5N1 or H5N6, which likely accounts for its relatively mild presentation.
The link and some excerpts from today's study follow. I'll have a bit more after the break.
Dispatch
Kenrie P.Y. Hui, John C.W. Ho, Ka-Chun Ng, Richard J. Webby, Malik Peiris, John M. Nicholls, and Michael C.W. Chan
Abstract
In 2024, influenza A(H5N1) genotype B3.13 viruses emerged from cattle and caused mild spillover infections in humans. Using human bronchus and lung tissue, we evaluated tropism, replication, and pathogenesis of 2 cattle influenza isolates.
Those viruses showed moderate replication competence and induced robust proinflammatory responses, suggesting potential risk for human health.
Highly pathogenic avian influenza (HPAI) H5N1 viruses remain a major global health concern, particularly because of sporadic spillover into mammals (1). HPAI A(H5N1) clade 2.3.4.4b viruses entered the United States through a trans-Atlantic introduction in late 2021, after which extensive reassortment among migratory birds produced the B3.13 and D1.1 genotypes. Those variants have spread widely, driving outbreaks in livestock and causing occasional human infections (2,3).
Beginning in 2024, H5N1 clade 2.3.4.4b viruses were detected in dairy cattle across multiple US states, and those infections were linked to mild zoonotic cases in humans (4,5). To assess the health risks of emerging cattle-origin influenza viruses, we examined tropism, replication, receptor use, and innate immune responses of cattle H5N1 viruses in human respiratory tract explants.
(SNIP)
Conclusions
Viral titers and influenza NP-positive cells demonstrated that cattle-origin H5N1/439 and H5N1/98638 strains are better adapted to human upper airway tissues than avian H5N1/483 and have similar replication abilities as H1N1pdm/415742 in human lung explants.
The ability to bind α(2–6)-linked SA further indicates a shift of receptor affinities that are more compatible with upper respiratory tissues. Innate immune responses of H5N1/439 and H5N1/98638 viruses in human lung tissue fell between those triggered by H1N1pdm/415742 and H5N1/483 viruses, indicating that cattle H5N1 viruses could pose a human health risk.
Defining how these strains infect human tissues and shape immune responses is critical for anticipating outbreaks and reducing zoonotic transmission risks. Because influenza viruses continually evolve across diverse avian and mammalian hosts, sustained research and surveillance remain essential to prevent human infections.
Dr. Hui is an assistant professor in the School of Public Health at the University of Hong Kong, China. Her research interests include risk assessment, understanding the pathogenesis of emerging respiratory viruses, and the development of therapeutic options for severe influenza diseases and coronavirus infections.While it appears that neither B3.13 or D1.1 currently have the ability to spark a pandemic, H5N1 continues to set new records in infecting mammalian hosts (see ISIRV: Update on H5N1 Panzootic: Infected Mammal Species Increase by Almost 50% in Just Over a Year).
These genotypes won't be the last iterations of H5N1, and while the future trajectory of HPAI is unpredictable, recent trends should give us pause.
And if we get lucky - and HPAI H5 should prove incapable of making that evolutionary leap - rest assured there's no shortage of other viral contenders in the wild.
