Preprint: Novel Highly Pathogenic Avian Influenza (A)H5N1 Triple Reassortant in Argentina, 2025

 

#18,735

The superpower of influenza A viruses is their ability for different subtypes to co-infect a host, swap genetic material, and generate a new `hybrid' virus; a reassortant.  This reassortment can generate new genotypes, or - if the HA and NA are involved - a new subtype. 

Some influenza subtypes are more prone to reassortment than others, with LPAI H9N2 often cited as one of the most promiscuous viruses currently known.  HPAI H5 is another, and in the 3 years since its arrival to North America  more than 100 genotypes have been identified.

Most these genetic changes do little to change the behavior of the virus, but over the past 14 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 18 states and mildly infecting dozens of humans
• 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.  In 2025 it was detected in dairy cows in at least 2 states.
• 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

H5N1 made its way to the South American continent in late 2022, and over the next twelve months spread from Columbia to Argentina (and beyond) via migratory birds and marine mammals. 

While much of what occurs in remote regions of the world with H5N1 often flies beneath our radar, somewhat surprisingly we've seen little evidence of new reassortants coming out of South America. 

That is, until today, with the publication of the following preprint on the bioRxiv server which describes the detection of a South American reassortant H5N1 virus collected earlier this year at a mixed backyard flock in Chaco province, northern Argentina.  

I've reproduced the abstract, and have included a few excerpts from the full report.  Follow the link to read it in its entirety.  I'll have a brief postscript when you return.

Novel Highly Pathogenic Avian Influenza (A)H5N1 Triple Reassortant in Argentina, 2025
Ralph E.V. Vanstreels, Martha I. Nelson, Maria C. Artuso, Luana E. Piccini, Vanina D. Marchione, Estefania Benedetti,Alvin Crespo-Bellido, Agostina Pierdomenico, Thorsten Wolff, Uhart, eAgustina Rimondi
doi: https://doi.org/10.1101/2025.05.23.655175

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Abstract

Genomic sequencing of re-emerging highly pathogenic avian influenza A(H5N1) virus detected in Argentina in February 2025 revealed novel triple-reassortant viruses containing gene segments from Eurasian H5N1 and low pathogenic viruses from South and North American lineages. These findings underscore continued evolution and diversification of clade 2.3.4.4b H5N1 in the Americas.

          (SNIP)

To our knowledge, this represents the first documented reassortment event between HPAI H5N1 and endemic South American LPAI viruses. The South American PB2 and PA segments are highly divergent from the rest of global AIV diversity (10) (Figure 1), suggesting that reassortment involving these genes has significantly expanded the genetic diversity of H5N1 polymerase segments.

Notably, although the H5N1-Arg_Feb2025 viruses have exchanged five gene segments, they retained the original Eurasian MP segment (Figure 2), which remains 100% conserved among H5N1 viruses circulating in North America. The absence of MP replacement by LPAI-derived segments, either in North or South America, suggests this MP segment may confer a selective advantage in HPAI H5 viruses.

Currently, there is no evidence of this novel 4:3:1 triple reassortant in other South American countries; however, should future detections confirm wider spread, classification as a new H5N1 genotype would be warranted.

           (SNIP)

In conclusion, our findings underscore the critical importance of sustained influenza surveillance coupled with whole-genome sequencing to track the evolution of HPAI H5N1 and support efforts to control and mitigate its impact on poultry, wildlife, and human health. Further research on the diversity of LPAI viruses circulating in Neotropical wildlife will be essential to understand potential interactions between H5N1 and South American lineage strains, and to assess the long-term consequences of the introduction of HPAI viruses into the region (and potentially beyond, should these reassortant strains spread to other regions). 

          (Continue . . . ) 

As the following FAO map (zoonotic avian flu reports since Oct 1, 2024) illustrates, reporting of avian influenza is pretty much limited to the United States, Southern Canada, Europe, and some parts of Southeast Asia. 

Vast swaths of Russia, China, South America, Africa and the Middle East rarely (if ever) report outbreaks, yet there is little doubt that (except for Australia/NZ) the virus is present in most of these non-reporting regions. 

We also learned last March - in Nature: Lengthy Delays in H5N1 Genome Submissions to GISAID - that the average delay for those countries which do submit non-human sequences to GISAID is 7 months, and that Canada came in last at 20 months.

A reminder that no news isn't necessarily good news - and given the limits of surveillance and reporting - we are always making decisions based on events that likely occurred weeks or even months ago.