Monday, December 29, 2025

Preprint: Emergence of D1.1 Reassortant H5N1 Avian Influenza Viruses in North America

 

#19,003

As we discussed at some length last August in H5Nx: Reassort & Repeat, in the Northern hemisphere millions of migratory birds spend their summers in their high latitude breeding areas in Alaska, Canada, Siberia, and even the Arctic.

During their stay, they hatch a new generation of (flu naive) fledglings while mingling with other species, potentially sharing avian viruses picked up the previous spring (see 2016's Sci Repts.: Southward Autumn Migration Of Waterfowl Facilitates Transmission Of HPAI H5N1).

These factors can lead to the creation and spread of new reassortants (genetic hybrids). While most are genetic failures - and unable to compete with existing strains - every once in a while a `new and improved' virus appears.


In the fall of 2024, while most `flu watchers' were concentrating on the B3.13 `bovine' genotype infecting hundreds of U.S. dairy herds (and mildly infecting dairy workers), a new, genotype (D1.1) emerged in wild birds, and swiftly crossed the country from west to east.



Unlike the `bovine' version, however, it produced a few severe (and 2 fatal) illness among a handful of human infections (see map above).  

D1.1 was also joined last fall by two `lesser' reported emerging genotypes (D1.2 and D1.3), the former found in infected pigs in Oregon, and the latter infecting an ostrich farm in Canada and producing a human case in Ohio.

Not to be outdone by B3.13,  D1.1 also spilled over into cattle (twice) in early 2025, with a 3rd spillover reported in Wisconsin early this month

Since its arrival to North America in 2021, more than 100 new genotypes have been identified, with scores more circulating in Europe, Asia, and South America. As flu viruses are notoriously promiscuous, new genetic combinations are certain to emerge. 

Most will be less `biologically fit' than their competitors, and will fall by the wayside, but occasionally a new, better adapted, variant will emerge. Although B3.13 and D1.1 currently have the bulk of our attention, they are simply stepping stones to the `next' viral iteration. 

All of which brings us to a new preprint, released last week, which describes what we know about this emerging genotype, including the swapping out of its NA gene (Eurasian neuraminidase with a North American LPAI N1), and the remarkable continent-wide dispersal of this strain. 

While D1.1 may not be ready for prime time, it continues to hone its abilities - mostly outside of our view - and that should give us pause. 

Due to its length, I've just posted the Abstract and a few excerpts. Follow the link to read the paper in its entirety. 

Emergence of D1.1 reassortant H5N1 avian influenza viruses in North America
Alvin Crespo-Bellido, Nídia S. Trovão, Alexander Maksiaev, Guy Baele, Simon Dellicour, Martha I. Nelson
doi: https://doi.org/10.64898/2025.12.19.695329
This article is a preprint and has not been certified by peer review [what does this mean?].


Preview PDF

Summary

Since 2021, highly pathogenic avian influenza viruses (HPAIV) belonging to H5N1 clade 2.3.4.4b have caused high mortality in North American wild birds and poultry. In 2025, a new D1.1 genotype caused two human deaths and host-switched to dairy cattle. However, the evolutionary origins and dynamics of D1.1 have not been fully characterized.
Here, our phylogenetic analysis of 17,516 H5N1 genome sequences uncovers how D1.1 introduced a major shift in the antigenic diversity and ecology of the H5N1 epizootic in North America.
D1.1 is the first major H5N1 genotype to (a) emerge in the Pacific flyway and spread west-to-east faster than any prior genotype; (b) antigenically shift via reassortment with the North American N1 segment, displacing the previously fixed Eurasian N1; and (c) transmit to a broader range of host species than any H5N1 genotype to date, introducing mammalian adaptations 


(SNIP)

Thus far, Eurasia has been a major source of H5N1 viruses for North America, and there is little evidence of D1.1, B3.2, or other dominant North American genotypes migrating back to Europe or Asia. However, H5N1 is routinely changing patterns. Understanding the risk that major evolutionary changes in H5N1 in the Americas presents to the rest of the world is a central question going forward. 

(Continue . . . )

There's an old joke about a tourist asking a NYC cabbie, `What’s the best way to get to Carnegie Hall?” and the cabby replies, Practice, practice, practice”.

In many ways, that applies to viruses. They usually get better (i.e. adapt) following repeated spillovers.  

And right now - in countless wild birds, poultry, cattle, pets, mammalian wildlife, and occasionally humans - it's getting a lot of practice.