Viruses: Novel Reassortant H5N2 Highly Pathogenic Avian Influenza Viruses from Backyard Poultry in Mexico

 

#19,081

Influenza A's superpower is its ability simultaneously infect a host with 2 or more strains, swap genetic material, and generate a new `hybrid' virus; a reassortant. This reassortment can generate new genotypes, or - if the HA or NA are swapped - a new subtype.

While flu viruses continually evolve slowly through antigenic `drift' - as we saw with H3N2 subclade K this past winter - truly large evolutionary jumps generally require reassortment (aka `Antigenic Shift').  

Most reassortants end up as evolutionary failures, but when they get it right, they can spark pandemics.  While rare, any virologist will tell you; `Shift happens.'

Twice in my lifetime (1957 & 1968) avian flu viruses did precisely that; reassorted with a seasonal flu virus and launched a human pandemic.

• The first (1957) was H2N2, which according to the CDC `. . . was comprised of three different genes from an H2N2 virus that originated from an avian influenza A virus, including the H2 hemagglutinin and the N2 neuraminidase genes.'

• In 1968 an avian H3N2 virus emerged (a reassortment of 2 genes from a low path avian influenza H3 virus, and 6 genes from H2N2) which supplanted H2N2 - killed more than a million people during its first year - and continues to spark yearly epidemics more than 50 years later.

When H5N1 arrived in North America 4 years ago it immediately began to reassort with local LPAI viruses, and in the first year generated at least 100 distinct genotypes. Since then, we've seen:

• In late 2023 a new B3.13 genotype emerged that could efficiently infect dairy cattle while mildly infecting scores of humans

• In the fall of 2024 we saw 3 new genotypes emerge (D1.1, D1.2, D1.3), with D1.1 producing more severe illness in humans. 

• We continue to see scattered reports of HPAI H5N5 in birds and mammals in Europe & Canada, and the the United States, and last fall we saw the first confirmed (and fatal) human infection.

This growing diversity of HPAI H5 can be seen everywhere the virus goes:

• South Korea is currently battling H5N1, H5N6, and H5N9. 

• Europe has their own distinct set of HPAI genotypes 

• A little over a year ago, in  Emerg. Microbes & Infections: Emergence of a Novel Reassortant HPAI Clade 2.3.4.4b A(H5N2) Virus, 2024, we looked at the emergence of a novel HPAI H5N2 virus in the Middle East. 

Due to limited surveillance and sharing of information, there are undoubtedly far more HPAI H5 reassortants circulating around the globe than we know. 

But today we get details on the recent emergence of HPAI H5N2 viruses - due to the reassortment of LPAI H5N2 and HPAI H5N1 - in backyard poultry across 3 Mexican states: Michoacán, Estado de México, and Ciudad de México.

This follows the announcement of the first known human infection with HPAI H5N2 (also in Mexico) last September. That was the third H5 case reported from Mexico since 2024, and the source of all three remain undetermined.

• The first occurred in April of 2024 (see Mexico announced the death of a 58-year-old man) when a patient - who also suffered from serious comorbidities - tested positive for LPAI H5N2, becoming the first laboratory-confirmed human case of influenza A(H5N2) infection reported globally.

• A year later (April 2025), a 3-year old girl from Durango State died following an H5N1 infection (see WHO DON Update On Mexico's Fatal H5N1 Infection).

Notably, this study found two distinct genotypes of HPAI H5N2, which supports the idea that reassortment activity is ongoing. The newer - more complex genotype (from Nezahualcóyotl and Gustavo A. Madero outbreaks) - most closely matches the human H5N2 case mentioned above.

I've only reproduced the abstract and an excerpt from the conclusion. Follow the link to read it in its entirety.  I'll have a bit more after the break.

Novel Reassortant H5N2 Highly Pathogenic Avian Influenza Viruses from Backyard Poultry in Mexico
Mario Solís-Hernández1,*, Guillermo Orta-Pineda1,*, Carlos Javier Alcazar-Ramiro1, Montserrat Amaranta Velázquez-Vázquez1, Claudia Garnica-Rivera1,
Marisol Karina Rocha-Martínez2, Nadia Carrillo-Guzmán1, Ignacio Eliseo Tetla-Zapotitla2, Israel Tiburcio-Sánchez1 … Armando García-López1
Viruses2026, 18(3), 337;https://doi.org/10.3390/v18030337
9 March 2026

Abstract

Highly pathogenic influenza A viruses of the H5 subtype continue to diversify worldwide through mutation and genetic reassortment, generating novel variants with unpredictable consequences under the One Health approach. 

Between 2024 and 2025, five outbreaks of avian influenza A viruses were detected in backyard poultry across Michoacán, Estado de México, and Ciudad de México. We conducted molecular and genetic characterization of five highly pathogenic H5N2 viruses isolated from these events. All cases tested positive for influenza A virus and the H5 hemagglutinin, exhibiting high pathogenicity with intravenous pathogenicity index values ranging from 2.88 to 3.0.

 Whole-genome sequencing revealed novel reassortants containing hemagglutinin from Eurasian H5N1 clade 2.3.4.4b and neuraminidase from the endemic Mexican H5N2 lineage. The viral genome of the isolate from Michoacán contained six segments derived from Eurasian H5N1 viruses introduced into North America in 2021–2022, while nucleoprotein and neuraminidase originated from Mexican H5N2 viruses. 

In contrast, viruses from Estado de México and Ciudad de México contained five H5N1-derived segments and incorporated polymerase basic protein 1, nucleoprotein, and neuraminidase from low-pathogenic H5N2 viruses circulating in 2024. Phylogenetic analyses confirmed the emergence of a distinct H5N2 Mexican sublineage, providing evidence of active viral reassortment and local evolutionary processes in Mexico.

(SNIP)

5. Conclusions

This study reports the emergence of novel H5N2 reassortant viruses in central Mexico, resulting from interactions between highly pathogenic H5N1 clade 2.3.4.4b and endemic low-pathogenic H5N2 lineages. The distinct genomic constellations identified, ranging from early-stage reassortants to more complex combinations involving PB1, NP, and NA, demonstrate active viral ex🔜→→change within backyard poultry systems. 

These findings emphasize the critical role of informal production environments as ecological niches that facilitate reassortment and sustain viral diversity. Mutational patterns in HA and NA further reveal ongoing adaptation and selective pressures consistent with extended regional circulation. 

The emergence of these reassortants underscores the urgent need to strengthen genomic surveillance programs, particularly in regions where influenza lineages overlap and biosafety measures are limited. Continuous monitoring will be essential to assess the evolutionary trajectory, pathogenic potential, and epidemiological impact of these viruses, as well as their implications for poultry health, zoonotic transmission, and pandemic risk.

       (Continue . . . )

The first known human H5N1 infections (n=18) were reported in Hong Kong in 1997. Seventeen years later (in 2014) we saw the 1st Known Human Infection With H5N6 Avian Flu Sichuan Province, China, and 7 after that (2021) we saw the first human infections with H5N8 in Russia.

  

While worrying, this relatively slow progress - averaging > 10 years between each new subtype spillover - has been somewhat reassuring. 

In contrast, over the past 6 months we've seen two new HPAI H5 subtypes spillover into humans for the first time; H5N2 in Mexico and H5N5 in the United States.  

Moreover, the interval between each new H5 subtype spillover (17 yrs ➡ 7 yrs ➡ 4 yrs) continues to shrink.

While all of this could be a coincidence, it's a trend we shouldn't ignore. The greater viral diversity in the wild, the better the chance that one of these novel viruses will crack the code, and spark the next global health crisis. 

And with our continued reliance on limited (and mostly passive) surveillance systems, our first clue may only appear after hospitals begin filling up with patients. 

Again.