#18,988
Last August, in H5Nx: Reassort & Repeat, we looked at HPAI's promiscuous ways, and its propensity to reinvent itself - via reassortment - after it meets up with compatible LPAI viruses.
Twenty years ago, H5N1's range was primarily limited to Southeast Asia, and so its reassortment opportunities were limited to LPAI viruses common to the region.
But a chance reassortment near Qinghai Lake, Tibet in 2005 produced a more biological `fit', and far more easily carried (by migratory birds) clade 2.2 of the virus (see H5N1 Influenza Continues To Circulate and Change 2006 by Webster et. al.), which led to the first major diaspora of the virus (eventually spreading to Europe, the Middle East, and Africa).
Over the years, as the virus spread around the globe, it encountered - and reassorted with - scores of different LPAI viruses, producing hundreds of new clades, subclades, genotypes, and even new subtypes (H5N5, H5N6, H5N9, etc.).
While many were biological failures, some proved competitive enough to advance the spread, evolution, and diversity of the virus. We saw huge changes to HPAI in 2014 (changeover to H5N8), in 2016 (the first major European Epizootic), and in 2017 the virus crossed the Equator on its way to South Africa.
As H5's range increased, so did its genetic diversity, giving it even more reassortment opportunities. While it was growing stronger, HPAI's first attempt to invade the Western Hemisphere (in 2014-2015) fizzled after 6 about months (see map below).
In 2020 the virus reassorted back to H5N1 - and having become even more `biologically fit' - in 2021 it make a far more successful 2nd invasion of the western hemisphere.
Remarkably, within months of arriving in North America, it had already generated more than 100 new genotypes, and for the first time became capable of infecting mammalian livestock (goats, cattle, alpaca, etc.)
The pattern has been pretty consistent; as HPAI spreads, it encounters new opportunities to increase its genetic diversity. It is one of the reasons why its recent spread to Hawaii, and its feared spread into Oceania, are of great concern.
Today we've a report from South America, published in the CDC EID Journal, which describes a unique 4:3:1 triple-reassortment of HPAI H5N1 detected in a mixed backyard flock (chickens, ducks, and turkeys) in Chaco Province, northern Argentina.
This outbreak was notable because the infected flock presented with severe, and atypical (dominated by diarrhea) symptoms. The authors wrote:
The predominance of gastrointestinal signs suggests possible shifts in tissue tropism or virulence. Also, the detection of a North American NP segment not previously identified in LPAI viruses from Argentina or elsewhere in South America highlights the need to strengthen regional AIV surveillance, even in the absence of active HPAI circulation.
I've posted the link, and some excerpts, from the dispatch below. Follow the link to read it in its entirety. I'll have a brief postscript when you return.
Volume 31, Number 12—December 2025
Dispatch
Novel Highly Pathogenic Avian Influenza A(H5N1) Virus, Argentina, 2025
Ralph E.T. Vanstreels, Martha I. Nelson, María C. Artuso, Vanina D. Marchione, Luana E. Piccini, Estefania Benedetti, Alvin Crespo-Bellido, Agostina Pierdomenico, Thorsten Wolff, Marcela M. Uhart, and Agustina Rimondi
Abstract
Genomic sequencing of reemerging 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 pathogenicity viruses from South and North American lineages. Our findings highlight continued evolution and diversification of clade 2.3.4.4b H5N1 in the Americas.
Highly pathogenic avian influenza (HPAI) viruses were introduced to South America in 2022 by migratory birds from North America. The viruses belonged to the 2.3.4.4b clade of HPAI A(H5N1) virus that became widespread in Europe in 2020 and spread to North America in 2021. The trajectory of H5N1 in South America has differed from H5N1 in North America in several critical ways. First, nearly all South America outbreaks stem from a single introduction of H5N1 viruses from North America (1,2), whereas the North America epizootic was reseeded by multiple independent introductions from Europe and Asia (A1–A6) (3,4). Second, South America H5N1 outbreaks were driven by a single genotype (B3.2) that was introduced from North America and remained genetically stable during its spread across South America. In contrast, H5N1 viruses in North America underwent frequent reassortment with low pathogenicity avian influenza (LPAI) viruses, prompting new genotype nomenclature (using B, C, D) (3). Third, South America’s H5N1 epizootic is unique in establishing mammal-to-mammal transmission in marine mammals, enabled by the H5N1 (B3.2) virus acquiring mammalian-adaptive polymerase basic (PB) 2 mutations (Q591K and D701N) (1,2). That pattern has not occurred in North America, where H5N1 spillover into terrestrial and marine mammals was transient, except in United States dairy cattle (3).
Beyond the ecologic devastation among coastal wildlife, in 2023, H5N1 (B3.2) virus spread widely in birds across mainland South America, leading to poultry and wild bird outbreaks (5–8). Although in 2024 HPAI outbreaks occurred in Brazil and Peru (World Organisation for Animal Health, https://wahis.woah.orgExternal Link), there were no detections in Argentina during March 2024–January 2025.
The Study
On February 11, 2025, Servicio Nacional de Sanidad y Calidad Agroalimentaria (SENASA; Buenos Aires, Argentina), Argentina’s national organization for agricultural health and safety, was notified of an outbreak in a mixed backyard flock (chickens, ducks, and turkeys) in Chaco Province, northern Argentina. The flock experienced high mortality (33/81 chickens, 37/99 ducks) in just 1 week. When we inspected the living flock, two thirds of the remaining 48 chickens had diarrhea and 1 of the remaining 62 ducks was lethargic; 2 turkeys were asymptomatic.
The household was located within a remnant fragment of the Dry Chaco biome, a hot and semi-arid tropical dry forest, surrounded by agriculture cropland. The affected flock had free access to a small pond frequently visited by wild waterfowl (Appendix 1). We depopulated and disinfected the area. We inspected backyard poultry within the 3 km perifocal zone (1 household) and the 3–10 km surveillance zone (7 households) and detected no illness or death. We did not find any affected wildlife on site.
(SNIP)
Conclusions
We have documented a reassortment event between HPAI H5N1 and endemic South America LPAI viruses. South American PB2 and PA segments are divergent from global AIV diversity (9) (Figure 1), indicating reassortment has expanded H5N1 polymerase diversity. Although the H5N1-Arg_Feb2025 viruses have exchanged 5 gene segments, they retained the original Eurasian MP segment (Figure 2), which remains conserved in most reassortant H5N1 viruses in North America. That segment conservation suggests the Eurasian MP segment might confer a selective advantage in HPAI H5 viruses. To date, we found no evidence of those novel 4:3:1 triple reassortant viruses in other South America countries; however, if future detections confirm wider spread, designation of a new H5N1 genotype would be warranted. Of consequence, genotyping tools such as the US Department of Agriculture’s GenoFlu should be expanded to include South American lineage genes for systematic classification of new virus genotypes.
(SNIP)
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. 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 effect on domestic animals, wildlife, and human health.
Dr. Vanstreels is a veterinarian and an associate researcher with the Karen C. Drayer Wildlife Health Center at the University of California, Davis. His research interests include South American and Antarctic wildlife health, with a special interest in the ecology and effects of highly pathogenic avian influenza H5N1 on wild bird and marine mammal populations.
As the following FAO map illustrates, there are large swaths of the globe where the HPAI virus is presumably circulating, but which provide little (or no) surveillance and/or reporting.
While many of these regions are impossibly remote, or lack the resources to do in-depth surveillance, there are many countries that simply choose not to report outbreaks for political or economic reasons.Blind spots include all of Russia, Central Asia, much of Africa, Northern Canada, and the interior of South America (note: Australia/NZ are testing, but the virus has not shown up yet).
And rightly so - because with rapidly evolving HPAI viruses - what we don't know can hurt us.
